Puromycin inhibition of eucaryotic ribosomes. Differences in sensitivity between polypeptide synthesis directed by endogenous mRNA and synthetic templates including poly(U). In a protein synthesis sytem derived from porcine uteri we have made the following observations: 1. Synthesis directed by the endogenous mRNA of the system is more sensitive to inhibition by puromycin than poly(U) directed synthesis. 2. Synthesis directed by the synthetic templates poly(G,U) and poly(C,U) is more sensitive to inhibition by puromycin than poly(U) directed synthesis and frequently shows a sensitivity to puromycin similar to that directed by endogenous mRNA. 3. Protein synthesis was inhibited by three aminoacyloligonucleotides (C-A-Phe, C-A-Asp, and C-A-Pro) which are analogs of the 3' terminus of aminoacyl tRNAs. Of the three, C-A-Phe was the most active and C-A-Asp the least active but, unlike puromycin, inhibition by these compounds was the same for endogenous and poly(U) directed synthesis. These results are interpreted as supporting the proposal that the acceptor site of ribosomes contains an hydrophobic binding region which interacts with the side chain of aliphatic amino acids, and particularly with the aromatic side chain of phenylalanine.


Single bilayer vesicles prepared without sonication. Physico-chemical properties. Single shelled lecithin vesicles of uniform size (diameter = 300 A) are prepared without sonication by solubilizing unsonicated lecithin dispersions with sodium cholate and removing the detergent from the mixed lecithin - cholate micelles by gel filtration on Sephadex G-50. A homogeneous population of pure lecithin single-bilayer vesicles free of multilamellar structures is obtained. The vesicle diameter is somewhat larger than the average diameter of sonicated vesicles. The curvature of the bilayer seems to be sufficiently large to allow for similar packing densities (areas/molecule) on the outer and inner layer of the bilayer. The morphology and some physico-chemical properties of these vesicles are described and compared with those of sonicated vesicles.


Haemagglutination of trypsin modified human erythrocytes by chagres virus.


Dose-response effects of beta-phenylethylamine on stereotyped behavior in pargyline-pretreated rats. We studied the dose-response and the time-course effect of beta-phenylethylamine (4.0-64.0 mg/kg, ip) on stereotyped behavior and motor activity in male Sprague-Dawley rats pretreated 2 hr eariler with pargyline (0.25-8.0 mg/kg, iv). Stereotyped behavior, defined as repetitive, nongoal-directed head movements and sniffing, and changes in motor activity were observed immediately after injection of beta-phenylethylamine for a 1 hr period. With increasing doses of pargyline pretreatment, beta-phenylethylamine produced, in a dose-response relationship, progressively more stereotyped behavior accompanied by increased motor activity. Without pargyline pretreatment, only 64.0 mg/kg beta-phenylethylamine induced behavioral changes. Stereotyped behavior and increased motor activity had an onset at 4-6 min after the injection of beta-phenylethylamine, peak at 10-30 min, and gradual decline in the next 10-20 min. These results are discussed in terms of a possible relationship with the degree of inhibition of Type a and Type B monoamine oxidase acused by the different doses of pargyline.


Influence of pyrazole on hepatic [1-14C] palmitate oxidation during acute ethanol intoxication. When studied at different times following ethanol intubation, the effects of pyrazole, administered to rats prior to ethanol, affects differently the alcohol-induced disturbances in hepatic [1-14C] palmitate oxidation. This peculiar time-course of the pyrazole induced effects supports the relationship between active ethanol oxidation and inhibition of hepatic fatty acid oxidation, but also emphasizes the caution which must be taken when using pyrazole to study "in vivo" the mechanisms involved in the alcohol induced fatty liver.


Screening for HBsag by hepanosticon in microplates.


Feasibility of sugar production from agricultural and urban cellulosic wastes with Trichoderma viride cellulase.


Cellulase production.

Cellulase production.


Purification of an exo-1,3-beta-glucanase from Candida utilis. An exo-1,3-beta-glucanase (EC 3.2.1.-) has been purified from the culture fluid of the yeast Candida utilis, and its biochemical properties have been studied. The amino acid analysis revealed a high content of acidic amino acids. The purified enzyme had 20% carbohydrate and a net negative charge showing higher affinity for laminarin than for p-nitrophenyl-beta-D-glucopyranoside and yeast cell-wall 1,3-beta-glucans. In addition, the enzyme hydrolyzed the substrates starting from the nonreducing ends, releasing glucose as the exclusive hydrolysis product. The enzyme activity was strongly inhibited by lactones and also by some heavy-metal ions.


Preliminary studies of pharmacological antigonism of anaphylaxis in the horse. Systemic anaphylaxis was induced in seven groups of ponies. Systemic hypotension, pulmonary hypotension, and apnea were observed in the control group. Suppression of anaphylaxis was achieved most efficiently with sodium meclofenamate followed by acetylsalicylic acid and diethylcarboamazine. Tripelennamine and methysergide reduced anaphylaxis minimally and burimamide not at all. The findings suggest that histamine and serotonin are of relatively low significance in equine anaphylaxis whereas kinins, prostaglandins and slow reacting substance may be more important.


Concentration of manganese in the tissues of cycling and anestrous ewes. A wide range of variation in concentration of manganese was found in the blood of 51 cycling ewes although no significant differences were evident (P less than 0.05) between days 4, 11 and 15 (day 0 = day of estrus) of the estrous cycle. In addition, no differences (P less than 0.05) were found in the manganese concentrations of various soft tissues of 15 ewes, killed on day 4 (five animals), day 11 (five animals) or during anestrus (five animals). The highest concentration of manganese was present in the liver, pancreas and kidney cortex, tissues which are rich in mitochondria. Among the tissues of the reproductive tract, the corpus luteum showed the highest manganese concentration and the level increased significantly (P less than 0.01) between days 4 and 11 suggesting that this trace element may be closely related to the metabolic and possible functional characteristics of this endocrine gland. Uterine horn and caruncles contained greater manganese concentrations than other components of the reproductive tract. The significance of these findings in relation to the effect of manganese intake on ewe fertility remains to be assessed.


Cardiological signs and symptoms in Friedreich's ataxia. The cardiovascular signs and symptoms were recorded in 36 patients with typical Friedreich's Ataxia (Group Ia, Ib). Seventeen patients were asymptomatic and this did not correlate with the severity of the disease. No pathognomonic clinical constellation was found to reveal the underlying cardiomyopathy.


Effect of locoweed (Astragalus ientiginosus) feeding of fetal lamb development. Locoweed, Astragalus lentiginosus, was fed to pregnant ewes for various periods during gestation. The principal gross effects on the developing fetuses were observed to be delayed placentation, decreased vascularization, fetal edema and hemorrhage, and alteration of cotyledon development. Deformed lambs and undersized lambs also occurred. Data from sheep fed locoweed during various periods of the entire gestation period are summarized and indicate that locoweed poisoning in the fetus as with the adult is a chronic type of intoxication. Also, poisoning of the fetus parallels poisoning in the dam.


Implications of participant observation in medical studies.


Thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura.


Immunochemical studies on the specificity of the peanut (Arachis hypogaea) agglutinin. The specificity of purified, peanut agglutinin has been studied immunochemically by quantitative precipitin and inhibition assays. The lectin showed substantial differences in precipitating with blood-group substances of the same specificity. Of the B substances tested, horse 4 25% completely precipitated the lectin, Beach phenol insoluble failed to interact, and PM phenol insoluble gave an intermediate reaction. The lectin did not precipitate with A1 substances, with hog gastric mucin A + H substance, or with A2 substance WG phenol insoluble. Another A2 substance, cyst 14 phenol insoluble, precipitated approximately 2/3 of the lectin. Of the H substances, Tighe phenol insoluble was inactive, JS phenol insoluble precipitated poorly, and morgan standard H precipitated about 80% of the lectin. However, first stage of Smith degradation, as well as Pl fractions obtained by mild acid hydrolysis of blood-group substances, gave products which precipitated strongly. The lectin was also completely precipitated by all precursor blood-group substances, as well as by cows 21 and 26, all having strong I-Ma, I-Ort, I-Step, and I-Da activities. Cow 18, which does not possess significant blood-group I activity, precipitated very slightly. Fractions of blood-group substances N-1 (Lea) and Tij (B) obtained by precipitation from 90 percent phenol at higher concentrations of ethanol interacted better with peanut agglutinin. These differences in activity are ascribable to a heterogeneity resulting from incomplete biosynthesis of carbohydrate side-chains of blood-group substances, particularly resulting in variations in the numbers of DGalbeta1 leads to 3DGalNAc or DGalbeta1 leads to 4DGlcNAc determinants. The agglutinin reacted with the hydatid cyst P1 glycoprotein, as well as with the previously studied antifreeze and sialic acid-free alpha1 acid glycoproteins, but not with pneumococcus type XIV polysaccharide. Inhibition of precipitation showed the lectin to be most specific for the disaccharide DGalbeta1 leads to 3DGalNAc, which is 14, 55, and 90 times as active as DGalbeta1 leads to 4DGlcNAc, DGal, and DGalbeta1 leads to 3DGlcNAc, respectively. DGalbeta1 leads to 3N-acetyl-D-galactosaminitol has approximately 1/25th the activity of DGalbeta1 leads to 3DGalNAc. Substitutions of DGlcNAc or LFuc on the DGal of active inhibitors completely blocked the activity, in line with the assumption that the combining site of the peanut lectin is a partial cavity. The oligosaccharides DGalbeta1 leads to 4DGlcNAcbeta1 leads to 6-hexane-1,2,4,5,6-pentol(s) and DGalbeta1 leads to 3[DGalbeta1 leads to 4DGlcNAcbeta1 leads to 6]N-acetyl-D-galactosaminitol showed the same inhibitory activity as DGalbeta1 leads to 4DGlcNAc, suggesting that the combining site of the peanut agglutinin may not be complementary to more than a disaccharide...


Autonomic innervation and plasma estradiol-17beta and progesterone levels in rats with subcutaneous ovarian autografts. Ovaries were removed from female rats and immediately autografted into a subcutaneous pouch in the flank in order to quantitate the relationship of graft re-innervation, steroid secretion and vaginal smear pattern. Animals were killed at thre time periods: three days after grafting, on the first day a cornified vaginal smear appeared and at the first metestrus. In addition, control animals were killed at metestrus. Plasma samples were obtained from all rats and analyzed for estradiol-17beta and progesterone concentration by radioimmunoassay. At the first day of vaginal cornification after grafting, plasma estradiol-17beta (45.8+/-4.0 pg/ml) was elevated in comparison to controls at metestrus (24.0+/-2.6 pg/ml), but plasma progesterone (21.5+/-4.0 ng/ml) was not different (30.6+/-1.7 ng/ml). Subsequently, at the first metestrus following grafting, plasma estradiol-17beta (23.0+/-3.5 pg/ml) was comparable to control values. In contrast, progesterone was decreased (17.5+/-1.9 ng/ml). A definite correlation was detected between the vaginal smear and plasma levels of steroid hormones in the castrated female rat with subcutaneous ovarian autographs Histochemical techniques were used to study the adrenergic and cholinergic innervations of grafts three days after grafting, at the first day of vaginal cornification, and at the first metestrus. No correlation was shown between density of adrenergic or cholinergic innervation and plasma levels of estradiol-17beta and progesterone or onset of a cycling vaginal smear.


An assay for sex hormone binding globulin based on affinity chromatography.


Phosphate compounds in the erythrocytes of newborns with ABO systems haemolytic disease. The following phosphate compounds of the erythrocyte acid-soluble fraction were subjected to chromatographic separation: ADP, ATP, adenylo-diphosphoglycerate, 2,3-diphosphoglycerate, hexose monophosphate, hexose diphosphate. In each of the fractions total phosphorus, and in fraction II inorganic phosphorus, were estimated. The material was derived from ten newborns with haemolytic disease as a result of ABO incompatability and from ten full-term healthy newborns, just after birth. The concentration of the compounds assayed, except for 2,3-DPG (the values in both groups were similar) was higher in the erythrocytes from affected newborns, but lower than that found in the material derived from the newborns with Rh incompatibility. It is suggested that the metabolism of erythrocytes of the newborns with haemolytic ABO disease may be somewhat different from that in Rh incompatibility cases because in the former the haemolysis is weaker, the anaemia is less pronounced and the tissue hypoxia is of a smaller degree.


Acquisition of human blood group antigens by Schistosoma mansoni. Juvenile forms of Schistosoma mansoni (schistosomula) have been cultured in human blood of various specificities and tested for the presence of blood group substances on their surfaces. The tests employed were survival following transfer into rhesus monkeys immunized against human blood substances, mixed agglutination reactions, and immunofluorescence. A, B, H AND Lewisb+ antigens were expressed at the surface when the parasites were cultured in blood of appropriate specificities. Rhesus, M N S, AND Duffy antigens could not be detected on the parasite surface following culture. The evidence suggests that the expressed blood group antigens are of host origin and are acquired by the parasite during culture, probably in the form of glycolipids or megaloglycolipids. It is likely that these substances are also acquired by parasites in the bloodstream of man. They may serve to mask surface parasite antigens, and so enable schistosomes to evade parasite-specific humoral or cellular immune responses.


The EMI whole body scanner in the demonstration of lymph node enlargement. Thirty-three cases with malignant disease due mainly to lymphoma and testicular tumours were evaluated by computerised tomography (CT) scanning on the EMI general purpose scanner. In many cases there were either more lymph nodes demonstrated than on lymphography or more disease shown in bone or the thorax than was suspected. CT scanning is particularly valuable in showing mesenteric, retrosternal, axillary and para-aortic lymph node enlargement. Bone, liver and pulmonary metastases were shown when not demonstrated by other methods as well as showing the extent of recurrence of malignant disease. In testicular tumours metastatic spread to paravertebral soft tissues behind the diaphragm was clearly demonstrated. This cannot be seen on lymphography. CT scanning appears to be the most accurate method to date of showing the extent of malignant disease, particularly in cases of lymphoma and testicular tumours.


Importance of behavioral assessment of the neonate.


The P blood group system in pigeon breeders and pigeon breeder's disease. A blood group P1-like antigen has been found in gram-negative bacilli isolated from pigeon droppings, in pigeon serum, and on pigeon red blood cells. As a probable resident of the environment of the pigeon loft, the antigen stimulated formation of anti-P1 antibody in eight of 11 pigeon breeders who belonged to the P2 blood group. Only one of 11 random hospitalized patients with the P2 blood phenotype had a detectable titer of anti-P1 antibody (P less than 0.01). The titer of anti-P1 antibody was not significantly different in symptomatic vs asymptomatic breeders. The presence or absence of anti-P1 antibody could not be correlated with any band of immunoprecipitates formed between pigeon breeder's serum and crude extract of pigeon droppings. The P antigen was identified in pigeon-dropping extracts of breeders with the P2 blood phenotype by inhibition of hemagglutination. We conclude that anti-P1 antibodies appear to be a component of the immunologic response to avian antigens of pigeon breeders but are probably unrelated to the pathogenesis of pigeon breeder's disease.


The status of prevention in the education of child psychiatrists. While the pioneers of modern child psychiatry focused much of their attention on prevention, the situation today is markedly different. A questionnaire survey of child psychiatric residency programs suggests that when attention is devoted to prevention in the education of child psychiatrists, it is often ambiguous, haphazard, and minimal. This impelled the authors to sample the current status of available knowledge about preventive child psychiatry with an assessment of the validity of the knowledge and its potential utility. These are followed by some suggestions for child psychiatric education.


The effects of prenatal and perinatal complications on development at one year of age. 35 variables descriptive of birth and obstetric complications, prematurity, maternal discomfort, and demographic status were studied for a sample of 322 infants. Factor analyses of these variables resulted in 7 major factors that were used to predict developmental status at 1 year of age for 233 of the subjects. Factors identified as "prematurity," "delivery and related variables," "ethnicity," and "complications" made significant independent contributions to Cattell DQ at 1 year. When Cattell DQs were corrected for the effects of gestational age, only delivery and related variables remained critical, confirming the importance of this factor for later development.


Mushroom poisoning.

Mushroom poisoning.


Effect of melatonin on the reproductive systems of male and female Syrian hamsters: a diurnal rhythm in sensitivity to melatonin. Hamsters were maintained on a long photoperiod (14L:10D) and were injected once daily with melatonin (10-25 mug) or sesame oil. Males which received melatonin during the afternoon (e.g., 6.5-13.75 h after lights-on) showed regressed testes and decreased levels of serum LH and FSH after several weeks of treatment. Injections of the oil vehicle or injections of melatonin given in the morning (3 h after lights-on) had no detectable effect on testicular size or on serum gonadotropins. Females which received melatonin during the afternoon became acyclic after several weeks of treatment and showed a diurnal pattern of LH secretion. The acyclic females required 4-6 weeks to resume estrous cyclicity following termination of the melatonin injections. The effects of melatonin on gonadal function and on serum gonadotropin concentrations in both sexes were similar to the previously observed effects of prolonged exposure to short photoperiods. These results indicate that chronic daily injections of melatonin can depress reproductive function in hamsters and that the effectiveness of the injections is dependent upon the time of day at which they are administered.


Total and free testosterone and total and free 17 beta-oestradiol in normally menstruating women. Estimations of plasma total and free testosterone (T) as well as of total and free 17beta-oestradiol (E2) have been performed in 6 normal women throughout the menstrual cycle. The plasma total T levels showed a small but significant cyclical variations, with significantly increased values around the midcycle (p less than 0.001). The pattern of free T during the cycle was similar to total T. Regarding total plasma E2, two typical peaks occurred, which were also observed in plasma free E2. Changes in testosterone-17beta-oestradiol binding globulin have not been detected throughout the menstrual cycle.


Significantly decreased apparently free testosterone levels in plasma of male homosexuals. Total and free plasma testosterone (T) were determined in male homosexuals. While total T showed no significant difference to a heterosexual control group, apparently free T in plasma was significantly lower (p less than 0.001) in 35 male homosexuals (mean +/- SD = 10.7 +/- 3.3 ng/100 ml) than in 38 male heterosexuals of similar age (13.3 +/- 4.5 ng/100 ml).


Mercury in Alaskan Eskimo mothers and infants. The potential danger of natural mercury accumulation in the diet of the Eskimo is evaluated through mercury levels determined in cord blood, placenta, maternal blood, hair, and milk of 38 maternal-infant pairs from Anchorage and the Yukon-Kuskokwim Delta. Although mercury levels are not discernably dangerous, trends to larger accumulations in maternal and fetal RBC and placental tissue with proximity to the sea and consumption of seals during pregnancy provide the basis for considering possible indicators of neonatal involvement. Mercury level in RBC from cord blood appeared as the best potential indicator of this involvement, although relationships with the mother's diet and level of mercury in the placenta also appear useful. In this area, average and maximal mercury levels in cord blood are 39 and 78 ng/ml, respectively, far below the acknowledged toxic level in infants of these mothers who eat seals or fish every day during their pregnancy.


[Congenital venous dysplasia of the right lower limb associated with Kasabach-Merritt syndrome in a 14 year old child. Successive destruction of the knee and hip. Conservative treatment].


Characterization and action of meiotic maturation inhibitors in starfish ovary.


The role of biotransformation in chemical-induced liver injury. The role of drug metabolism in chemical-induced liver injury is reviewed. Parameters for studying the formation of chemically reactive metabolites are discussed and the factors that alter the formation and covalent binding of reactive metabolites are selectively emphasized. Some of the experimental work that led to these concepts is discussed, especially the chemical toxicology of the hepatic injury produced by acetaminophen, bromobenzene, furosemide, isoniazid and iproniazid.


Differential effects of lectins mediating erythrocyte attachment and ingestion by macrophages.


Nuclear proteins. III. The fibrillar nature of the nuclear matrix.


The effect of inhibitors of microtubule and microfilament function on the cellular slime mould Dictyostelium discoideum.


Is the movement of single cells within solid tissue masses induced by trypsinization?


Serial lateral hypothalamic destruction: infancy and adulthood.


Functional alterations of liver mitochondria in chronic experimental alcoholism.


Chemical modification of liver alcohol dehydrogenase with alpha-bromo-beta-(5-imidazolyl) propionic acid.


Polymerization of a major surface-associated glycoprotein, fibronectin, in cultured fibroblasts.


The occurrence of a new type of proteochondroitin sulfate in the developing chick embryo.


The effect of an extraluminal transducer on the reproductive capability of the rabbit. An extraluminally attached microminiature force transducer, designed for reproductive tract contractility measurements, was investigated in terms of its effects on the physiology of the uterotubal junction in the rabbit. The presence or attachment process of the extraluminal force transducer (EFT) did not affect the rate of pregnancy or the number of embryonic implantation sites whether the attached device was silicone rubber or polyethylene-encased. The uterotubal junction was able to retain the blastocyst for the required time after mating, while an examination of postembryonic mortality revealed a rate of one resorption in some experimental groups. The gestation period was unaffected by the EFT, ranging from 30 to 40 days with a mode of 32, while histologic examinations revealed formation of a thin fibroblastic layer, some increased vascularity, and no abnormal leukocytic accumulation.


The specification of fertility planning status. The principal obstacle to accurate measurement of fertility planning intentions in cross-sectional surveys is the disposition of the respondent to provide the interviewer with a reconstruction of the couple's history which departs more or less from what actually happened... Since married couples in America are now close to effective planning of fertility, the future of reproduction in the United States will depend much more than in the past on reproductive intentions. From this viewpoint, the uncertainty of reproductive intentions as shown here suggests extreme circumspection in using current reproductive orientations for future projections.


Solubilization and peptide "mapping" of a large external glycoprotein fraction labelled by lactoperoxidase-catalysed iodination of cultured fibroblasts.


Biosynthesis of phosphatidylcholine and phosphatidylethanolamine by germinating soya bean.


Cholesterogenesis from tritiated water in rats: evidence against the existence of diurnal rhythms (1. Temporal effects).


Changes in lipogenesis during mammary-gland development.


Glycolipid synthesis in hamster embryo cell cultures.


Cholesterogenesis from tritiated water in rats: evidence against the existence of diurnal rhythms (2. Effect of meal-feeding).


Effect of histidinol on the initiation and elongation of protein synthesis in Krebs II ascites cells.


Nitrogen metabolism in the photoresponsive phytopathogenic fungus Cercospora beticola.


Carbon-utilization patterns in the photoresponsive fungus Cercospora beticola.


Effect of polyinosinic acid-polycytidylic acid on establishment, and on spontaneous and chemical transformation of Balb/c mouse-embryo cells in culture.


The male climacteric.

The male climacteric.


Comparative studies on clinical, morphological and biochemical parameters in andrology.


The effect of endometrial cells on the growth and expansion of rabbit blastocyst in vitro.


Synthesis of LDH-1 during mamalian oogenesis and early development.


Enhancement of differentiation of lens and pigment cells by ascorbic acid in cultures of neural retinal cells of chick embryos.


Cytogenetic analysis of oocytes and early preimplantation embryos from XO mice.


The structural gene for alpha-mannosidase-1 in Dictyostellium discoideum. We have isolated 4 independent mutations affecting alpha-mannosidase-1, a developmentally regulated activity in Dictyrostelium discoideum. Three of these result in a thermolabile alpha-mannosidase-1 activity. One mutation also affects the substrate affinity (Km) of the activity. In diploids these mutations show a gene dosage effect and are all alleles. The structural gene for alpha-mannosidase-1, as defined by these mutations, defines a new linkage group, linkage group VI. alpha-mammosidase 1 is probably a homopolymer with subunits of 54,000 daltons. We have also mapped two temperature-sensitive-for-growth mutations onto two previously defined linkage groups.


Male meiotic behaviour and male and female litter size in mice with the T(2;8)26H and T(1;13)70H reciprocal translocations.


The use of sperm-specific lactate dehydrogenase isoenzyme for the identification of semen in dried stains. The sperm-specific lactate dehydrogenase (LDH) isoenzyme (Blanco and Zinkham, 1963; Goldberg, 1963) separated from other LDH isoenzymes of semen by polyacrylamide gel electrophoresis has been found to be suitable for specific differentiation of human semen from other human body fluids and semen of commonly encountered animals. Seminal isoenzymes were found to be stable even 4 weeks after storage in tropical conditions. The method gave substantially more positive results than microscopic identification of spermatozoa when applied to a large number of relatively old stains on actual crime articles. It is therefore valuable in a large number of cases involving normal males and also in interpreting results of immunological and enzymological individualisation of semen stains.


An ultramicroscopic study on rigor mortis. Gastrocnemius muscles taken from decapitated mice at various intervals after death and from mice killed by 2,4-dinitrophenol or mono-iodoacetic acid injection to induce rigor mortis soon after death, were observed by electron microscopy. The prominent appearance of many fine cross striations in the myofibrils (occurring about every 400 A) was considered to be characteristic of rigor mortis. These striations were caused by minute granules studded along the surfaces of both thick and thin filaments and appeared to be the bridges connecting the 2 kinds of filaments and accounted for the hardness and rigidity of the muscle.


Immunogenicity of "single component" port insulin. Twelve diabetic subjects who were not previously treated with insulin were divided into two groups of six each. Group I was treated with single component pork insulin and Group II was treated with standard (USP) insulin for 5 to 10 months. Three out of six in Group I, and five in Group II, developed circulating insulin antibodies. Daily insulin requirement in the two groups were almost the same. Insulin antibody titer did not fall in three insulin-treated diabetic subjects when single component pork insulin was substituted for USP beef-pork insulin. This study shows that the single component insulin is antigenic in human subjects.


Endometrial blood flow in rats.

Endometrial blood flow in rats. The endometrial blood flow was measured in rats by injections of 85Kr saline into aorta and measurements of the clearance of the radioactivity by a Geiger-Müller probe situated in the uterine lumen. Estrus and diestrus were determined by vaginal smears. The endometrial blood flow was found to be 0.88 +/- 0.08 (mean +/- SEM) ml/g tissue/min in estus and 1.60 +/- 0.15 mg/g/min in diestrus. The experiment indicates that the endometrial blood flow and the total uterine blood flow change in opposite directions during the estrous cycle.


Testosterone production by ovarian follicles of the domestic cat (Felis catus). In order to determine whether the ovarian follicles of the domestic cat which normally ovulates following copulation, were similar to those of the rabbit steroidogenically, the following experiments were carried out. Follicles were dissected out of ovaries from nine estrous cats throughout the year and incubated in medium alone or with luteinizing hormone (LH) or human chorionic gonadotropin (HCG). Media were removed every 15 min and stored frozen until analyzed for testosterone using established radioimmunoassay procedures. Although LH and HCG caused slight increases in testosterone production the amounts produced were much less than that produced by rabbit follicles under identical conditions. However, when follicles were incubated for a total of 8 h without removal of media, marked changes in testosterone and estradiol production occurred. These data suggest that the ovarian follicles of the estrous cat are steroidogenically active.


The use of 8-anilino-1-naphthalenesulfonic acid as a reporter group molecule for circular dichroism and fluorescence measurements. The effect of stearic acid and sodium dodecylsulfate on the conformation of bovine and human serum albumin. The fluorescence probe ANS(8-anilino-1-naphthalenesulfonic acid) was employed as a reporter group molecule for circular dichroism and fluorescence measurements in order to investigate the effects of stearic acid and sodium dodecylsulfate on the conformation of bovine and human serum albumin. Stearate as well as dodecylsulfate displaces ANS from the binding to both albumins. Besides this displacement, stearate and dodecylsulfate influence the fluorescence properties and the extrinsic Cotton effects on ANS bound to both albumins. It is suggested that the origin of these effects is a microdisorganization of the albumin structure, provoked by the binding of stearate and sodium dodecylsulfate. Each of the four extrinsic CD bands of bound ANS was influenced in a different manner by the addition of stearate and dodecylsulfate. Using the data of the fluorescence measurements and of the circular dichroism measurements it was possible to differentiate the effects of one ligand on both albumins and of both ligands on one albumin more efficiently than would have been possible using one of the two methods alone. It is suggested that the use of ANS as a reporter group molecule for fluorescence and circular dichroism measurements is a very good tool to detect small changes in the environment of ligand binding sites on protein molecules.


Abnormal behaviour of proline in the isothiocyanate degradation. It has been observed that proline residues often initiate overlaps during sequenator analysis. The cause has been shown to be an abnormally slow cleavage reaction. The kinetics of the cleavage reaction has been studied and found to obey pseudo-first-order kinetics. There are considerable differences in reaction rates depending on the position of proline in the sequence, as demonstrated for the four prolines in the N-terminal section of the H2B histone from chicken.


Activity of nuclear DNA-dependent RNA polymerases in mouse limb buds differentiating in vivo or in organ culture. 1) A method was developed to measure the activity of DNA dependent RNA polymerase reactions I (alpha-amanitin-insensitive) and II (alpha-amanitin-sensitive) in homogenates of very small amounts of tissue. This technique was used to study the activity of these polymerase reactions in limb buds from mouse embryos developing in vivo or in an organ culture system. This culture system allows the morphogenetic differentiation of limb buds in early stages of embryonic development (day 10-11 of gestation greater than or equal to 37 - 45 pairs of somites) from a blastema stage to well recognizable cartilaginous bone analgen. 2) An increase in the activities of both types of RNA polymerases was found to occur in vivo in limb buds on day 12 of gestation when compared with the activity measured on day 11 of gestation. A similar increase with a maximum about 24-48h after initiation of the cultures could be observed in the explants differentiating in organ culture. To our knowledge this is the first time that induction processes proceeding in mammalian embryonic tissues could be correlated with an increased activity of RNA polymerases. 3)A rough estimate shows that the rate of transcription due to RNA polymerase I measured in homogenates or in isolated nuclei (measured with substrate concentrations giving about 80% of the maximal rate) would account for the assumed rate of rRNA synthesis in vivo. The measurement of the RNA polymerase activity in isolated nuclei, thus, may give some information about the transcriptional processes occurring under "physiological" conditions. 4) The mammalian organ culture system presented provides a suitable model for studying embryonic differentiation processes.


Identification of the acid-stable trypsin-plasma inhibitors of the human and bovine serum as Kunitz-type inhibitors. Preliminary sequencing data.


Cysteine residues mark the C-terminal triple-helical/non-triple-helical junction in type III collagen.


Analysis of volatile N-nitroso compounds by combined gas chromatography and thermal energy analysis.


Constitutional chromosomal breakage.

Constitutional chromosomal breakage. There were 18 individuals found to have a constitutional chromosome fragility causing an increase in break frequency. For each chromosome the breakpoint is always the same, whether it involves chromosomes from the same person, the same family, or different families. The fragile points are bands 10q24, 12q13, 16q21, 17p12, and Xq27. Autosomal constitutional fragility does not seem to have a phenotypic correspondence. They were found mostly in parents of children with chromosomal abnormalities or in couples with a history of repeated spontaneous abortions which permits one to raise the possibility of an interchromosomal effect. The six constitutional chromosomal fragilities of the X chromosome had in common the association of mental deficiency, delayed speech, and large malformed ears. The break points in constitutional chromosomal fragility were compared to those of spontaneous breaks in vitro, to those induced by X-rays, and to those in Fanconi's anemia. The theoretical  consequences of these structural abnormalities are discussed as well as what to do about them when they are found.


Volatile nitrosamines in fried bacon.

Volatile nitrosamines in fried bacon. Higher levels of NPy and NDMA in cooked bacon and its cooked-out fat were associated with those cures which contained higher levels of nitrite, but no correlation between nitrosamine concentrations and initial nitrate levels was observed. There was a higher proportion of nitrosamines in cooked-out fat than in cooked bacon, but by far the greatest amounts were lost in the vapours produced during cooking.


Determination of eight volatile nitrosamines in thirty cured meat products with capillary gas chromatography-high-resolution mass spectrometry: the presence of nitrosodiethylamine and the absence of nitrosopyrrolidine. Five samples each of six cured meat products were analysed for the presence of eight volatile nitrosamines. A combined steam distillation-extraction step at pH 8-9 plus a concentration step were used for preparation of extracts. These were analysed, without further clean-up, using a coupled capillary GC-HRMS system at a resolution of 4 000. The MS was used in the fixed mass mode, but after the retention time of each nitrosamine the mass adjustment was tuned to the mass of the next nitrosamine. This combination allowed not only an unambiguous identification of the nitrosamines but also their direct quantitative determination. The products investigated were cooked ham, fermented sausage, raw bacon, mildly fried bacon, fried minced mean and smoked meat. Only one nitrosamine, NDEA, was sometimes found to be present in relatively large amounts. It occurred in two of the bacon samples; the concentration increased during mild frying from 4 and 13 mug/kg to 16 and 43 mug/kg, respectively. It was also present in two of the smoked meat samples in amounts of 7 and 91 mug/kg, respectively. Its identity was further confirmed on a second and third capillary column also coupled to the MS, and by direct introduction of the extracts into the MS at a resolution of 15 000. A silicon compound with practically the same retention time and mass as NDMA, which originates from the antifoam agents used as shown by other investigators, was found in the extracts in amounts corresponding to abuot 2 mug/kg of product. Nevertheless, seven samples were found positively to contain NDMA in amounts of 2-6 mug/kg. NMEA, NMPA, NMBA and NDPA could not be detected in any of the samples, nor could NPip or NPy. That no NPy (i.e., less than 50 mug/kg) was found in the fried bacon samples may be due to the mild frying method used. The use only of capillary GC with a nitrogen-selective detector, without further sample clean up, would have led to many false-positive results due to the presence of other nitrogen-containing compounds.


Nitrosamines in cured meat products.

Nitrosamines in cured meat products. One hundred samples of specially selected spiced meat products (sausages, salami, bologna, wieners, meat loaf, canned luncheon mean, etc) were analysed for nitrate, nitrite and volatile nitrosamines. None of the samples contained high levels of nitrosamines, but many contained traces, generally in the range from 2-50 mug/kg. Some contained as many as four nitrosamines, namely, NDMA, NDEA, NPip and NPy. In a few cases the samples were reanalysed after two weeks' storage at 4 or -20 degrees C, but no significant change in the nitrosamine levels could be detected. The identity of the nitrosamines was confirmed by GLC-high-resolution-MS.


Quantitative and qualitative determination of some volatile nitrosamines in various meat products.


Identification and quantitative determination of nitrosoproline and nitrososarcosine and preliminary investigations on nitrosohydroxyproline in cured meat products. A method for the quantitative determination of certain nonvolatile N-nitrosoamino acids has been developed. After a clean up procedure, using liquid-liquid extraction and ion exchange separation, the nitrosoamino acids are determined either by GC after conversion to their methylesters or by photolysis and subsequent determination of formed nitrite ion. Identification is made by GC-MS. Nitrosoproline and nitrososarcosine can be determined unambiguously; work on nitrosohydroxy-proline is in progress. Analysis of some cured meat products has shown that nitrosoproline may be present in relatively large amounts (340-440 mug/kg, confirmed by GC-MS) as compared to the amounts of volatile in notrosamines commonly found in these products. A trace of nitrososarcosine (about 10 mug/kg) was found in one product.


The relation between the determinable quantities of volatile N-nitroso compounds and the peroxide number in soya bean oil. Comparative studies of soya bean oil with and without addition of N-nitroso compounds (NDMA and NDEA) at different hydroperoxide concentrations have shown that the determinable quantities of substances having the retention time of N-nitroso compounds in soya bean oil and of nitrosoamines added to the oil are dependent upon the peroxide number. The determination was carried out by gas chromatography (nitrogen detector, nitrogen-sensitive, flame-ionization detector) prior to and following irradiation with UV light (360 nm). When the peroxide number was above 4, the determinability and the recovery were reduced by more than 60 per cent. In advanced autoxidation and after reduced recoveries, large amounts of NMDA and NDEA may be encountered for a short time. A possible linkage between N-nitroso compounds and peroxide is discussed. Comparative investigations of soya beans, crude oil, intermediates and commercially available steamed oils have revealed that the concentrations of the compounds with NDMA and NDEA properties in crude oil (peroxide number about 3) is higher than in soya beans. The recovery of these compounds is very poor in intermediate products with high peroxide numbers (about 5 to 9). However, N-nitroso compounds can be demonstrated in commercially available oils treated with steam (peroxide number about 0.7), although to a lesser extent than in crude oil.


Nitrosamines and their precursors in some Estonian foodstuffs.


Reduction of nitrosodimethylamine content in Cantonese salt fish.


Group evaluation of volatile and nonvolatile N-nitroso compounds in foodstuffs.


Techniques for the screening of foodstuffs for volatile nitrosamines.


Public interest report No. 20--Why shouldn't providers and consumers (older people and their families) join together in an alliance for older people?


Incorporation of U-[14C]-lysine into p=otein, and DNA, RNA, protein and glycogen contents in the uterus of heat-acclimatized rats during the estrous cycle.


Malnutrition, humoral immunity and infection.


Lissencephaly in Lhasa Apso dogs.

Lissencephaly in Lhasa Apso dogs.


Prevalence of Toxoplasma infection in cattle slaughtered at an Ohio abattoir. Specimens of heart, diaphragm and, in 159 instances, esophagus were taken from 352 cattle slaughtered in an Ohio abattoir. The total weight of the material was 32 kg, and this was fed to 12 specific-pathogen-free cats to test for Toxoplasma infectivity. None of the 12 cats acquired Toxoplasma infection, as evidenced by their failure to excrete oocysts or to develop antibodies, and by failure to isolate Toxoplasma from their tissues by inoculation into mice. In further tests, a 650-g sample of beef from 77 of the 352 cattle was digested in 1% trypsin, then inoculated intraperitoneally into 40 mice. Toxoplasma was not isolated from the mice. Serums from 186 of the 352 cattle were inactivated at 60 C for 1 hour, then examined by the Sabin-Feldman (dye) test for antibodies to Toxoplasma. None had titers of more than 1:8. Of the 186 serums, 77 were also examined for antibodies in the indirect hemagglutination test. One had a titer of 1:64, which was considered nonspecific. Thus, evidence for Toxoplasma infection was not found in 352 cattle.


Adiaspiromycosis in the lungs of a dog.

Adiaspiromycosis in the lungs of a dog.


A serologic survey of a population of Georgia dogs for Brucella canis and an evaluation of the slide agglutination test. In a serologic survey of stray and pet dog populations of Georgia, serums were screened for Brucella canis antibodies, using the slide agglutination test. If results were positive, B canis antibody titers were determined, using the standard tube agglutination test. The stray dogs had significantly (P less than 0.01) higher titers than did the pet dogs. The reactor rate was 58% higher for the slide agglutination test than for the tube agglutination test. The manufacturer's  evaluation of the slide agglutination test was based on a comparison of the serologic results of that test with those of the tube agglutination test, using a comparative method that permitted the results to be interpreted as 99% agreement between the 2 tests. Reevaluation of the manufacturer's data by a different method indicated that the slide agglutination test is very accurate when the results are negative (99.7% specific) but less so when the results are positive (62.5% sensitive).


Evaluation of a modified water-deprivation test for diagnosis of polyuric disorders in dogs. A modified water-deprivation test was performed on 12 polyuric and 4 clinically normal dogs. Immediately after maximal urine osmolality had been achieved with water deprivation, antidiuretic hormone was injected to test further renal concentrating ability. The test provided accurate diagnosis of severe hypothalamic-neurohypophyseal diabetes insipidus in 3 dogs, partial diabetes insipidus in 2 dogs, and primary (psychogenic) polydipsia in 2 dogs. Five polyuric dogs with hyperadreno corticism had a response to the modified water-deprivation test similar to that of dogs with partial diabetes indipidus.


Genetic influence on normal variability of maximum expiratory flow-volume curves. To determine the importance of genetic influence on the variability of maximum expiratory flow-volume (MEFV) curves in normal individuals, MEFV curves breathing air and a mixture of 80% helium and 20% oxygen (He-O2), lung volumes, specific airway conductance, and closing capacity (CC) were obtained in 10 pairs of identical and 6 pairs of nonidentical twins, all nonsmokers and asymptomatic. For a given pair of identical twins, MEFV curves on air were more similar than those of a pair of nonidentical twins (P less than 0.02). The intrapair differences of identical twins were smaller than nonidentical twins of maximum expiratory flow (Vmax) at 60% of total lung capacity (TLC) on air (P less than 0.001) and on He-O2 (P less than 0.01). However, intrapair differences of Vmax at 40% TLC and CC were not significantly different in the two groups. Since Vmax at 60% TLC on air and He-O2 are dependent on the geometry of large airways these findings are suggestive that the geometry of large airways may be related to genetic factors. The relationship of the geometry of the peripheral airways and genetic factors has not been defined.


Scanning electron microscopy of the endometrium during the secretory phase. Scanning electron microscopy was used to study the surface morphology of the rabbit endometrium during the secretory phase of the oestrous cycle. The free surfaces of ciliated and of inactive active secretory cells are described. Changes in secretory cell surface morphology resulting from accumulation and secretion of material involve the apparent retraction of microvilli and the formation of one or more bulbous protrusions of the cell's apical surface. These protrusions may be relatively smooth surfaced or exhibit long  slender micro-extensions. The protrusions grow in size and are eventually pinched off. Loss of the bulbous protrusions often leaves behind crater-like invaginations of the cell's surface. Secretory cells adjacent to the endometrial glands are the first to exhibit signs of mucin accumulation and secretion. The single cilium of a secretory cell is not apparently affected by the secretory process. Signs of ciliated and secretory cell degeneration, and possible sloughing, are also described.


Molecular weight estimation of protoheme ferro-lyase by radiation inactivation. The molecular weight of protoheme ferro-lyase [EC 4.99.1.1], a mitochondrial enzyme, was estimated by the radiation inactivation method. Irradiation in vacuo caused less inactivation than that in air. The approximate molecular weight determined by this method was in the range from 250,000 to 320,000. The significance of the location of the enzyme in connection with its role in heme synthesis is discussed on the basis of Singer's membrane theory.


Biosynthesis of glycosphingolipids in cultured mouse neuroblastoma cells. Precursor-product relationships among sialoglycosphingolipids. The reaction sequence for the biosynthesis of gangliosides by mouse neuroblastoma cells has been investigated by studying the pattern of incorporation of labeled precursors into sialoglycosphingolipids. Cultured NB41A cells incorporated N-[3H]acetylmannosamine into the sialic acid moiety of GM3 in less than 10 min. Labeled GM2 was not detected in cells incubated for less than 30 min, while measurable radioactivity did not appear in GM1 until after 60 to 90 min. Analogous experiments were carried out using [14C]galactose. No significant amount of labeled hexose was incorporated into asialo-GM2 during 60 min of culture. These studies are in accord with results of previous studies on glycosyltransferases of NB41A cells (Kemp, S. F., and Stoolmiller, A. C. (1976), J. Neurochem. 26, 723-732), and further support the concept that the pathway of synthesis of gangliosides proceeds via GM3 leads to GM2 leads to GM1.


The zygosity of twins: further evidence on the agreement between diagnosis by blood groups and written questionnaires.


Conformational constraints in nuclear DNA. We have investigated DNA superstructure in a wide range of nuclei of higher cells by gently lysing cells to release structures that resemble nuclei but are depleted of nuclear proteins. The sedimentation properties of these structures, which we call nucleoids, have been examined in sucrose gradients containing the intercalating agent, ethidium. The sedimentation rate of nucleoids derived from the growing cells of mammals, birds, amphibians and insects varies in the manner characteristic of circular and superhelical molecules of DNA. These characteristic changes in sedimentation rate are abolished by irradiating the nucleoids with low doses of gamma-rays, a procedure known to introduce single-strand scissions into DNA. We have also investigated by similar means DNA superstructure in nucleoids derived from a variety of different chick cells. Nucleoids derived from adult hen erythrocytes differ from the other nucleoids studied in that their sedimentation rate does not vary in the manner characteristic of supercoiled DNA.


Ultrastructural studies on the surface membrane of the mouse egg. Fertilized and unfertilized mouse eggs were examined by scanning and transmission electron microscopy for evidence of mosaicism in the organization and concanavalin A-binding properties of their surface membranes. No obvious quantitative mosaicism in concanavalin A binding was noted. The egg membrane was microvillous over most of its surface, but was smooth in the region overlying the 2nd metaphase spindle of the unfertilized egg and on the polar body of the fertilized egg.


Contacts between pigmented retina epithelial cells in culture. The behaviour of primary cultures of dissociated embryonic chick pigmented retina epithelial (PRE) cells has been investigated. Isolated PRE cells have a mean speed of locomotion of 7-16 mum/h. Collisions between the cells normally result in the development of stable contacts between the cells involved. This leads to a gradual reduction in the number of isolated cells and an increase in the number of cells incorporated into islands. Ultrastructural observations of islands of cells after 24 h in culture show that junctional complexes are present between the cells. These complexes consist of 2 components: (a) an apically situated region of focal tight junctions and/or gap junctions, and (b) a more ventrally located zonula adhaerens with associated cytoplasmic filaments forming a band running completely around the periphery of each cell. The intermembrane gap in the region of the zonula is 6-0-12-0 nm. The junctional complexes become more differentiated with time and after 48 h in culture consist of an extensive region of tight junctions and/or gap junctions and a more specialized zonula adhaerens. It is suggested that the development of junctional complexes may be responsible for the stable contacts that the cells display in culture.


Bromination products of 2,4-dimethyl-1,5-benzodiazepine.


Some derivatives of 2- and 3-phenylthiophen.


Synthesis and crystal and molecular structure of a 1,11-methano-steroid, 3-methoxy-1'beta-methyl-1,11alpha-methano-9beta-estra-1,3,5(10)-trien-17beta-ol.


Syntheses of isoalloxazines, alloxazines, toxoflavins, and Fervenulins by oxidative cyclization of the Michael-type adducts from substituted 6-Aminouracils and Azo-compounds.


Structures of three new C16 terpenoids from an Acrostalagmus fungus.


Mechanism of aromatic hydroxylation in fungi. Evidence for the formation of arene oxides.


Derivatives of hydroxyquinol. Part 4. A synthesis of di-O-methylcitromycin; Electronic effects in hydroxyquinol derivatives.


Determination of biogenic amines in intestinal contents by ion-exchange chromatography.


Preferential binding of testosterone over epitestosterone by human plasma. The main purpose of this study was to investigate if the specificity of the binding of testosterone to plasma proteins could be defined as a preferential binding of this steroid over epitestosterone. The amount of testosterone that is specifically bound was calculated using the formula: (see article) concentration, where "Ri" is the ratio (14C) testosterone: (3H) epitestosterone in plasma prior to centrifugation, "Ru" is the isotope ratio in the protein-free supernatant obtained after ultracentrifugation (149,000 x g, at 0 C, for 18 h) and "T concentration" is the testosterone concentration in plasma resulting from addition of (14C) testosterone, the endogenous steroids having been removed by preliminary charcoal extraction. The theoretical separation of the binding sites for testosterone into two populations, one non-specific with no preference for testosterone over epitestosterone, and another with absolute specificity for testosterone over its physiologically inactive stereoisomer, proved to be useful. Ovalbumin was found to be an example for non-specific, non-preferential binding. Determination of the ratio (14C) testosterone: (3H) epitestosterone in the successive fractions of various ultracentrifuged preparations showed a small but significant preference for (14C) testosterone by human and bovine serum albumin, while alpha1-acid glycoprotein had a preference for (3H) epitestosterone. Saturation curves showed at least two components: the first one, presumably corresponding to TeBG, had a higher affinity and lower capacity. This binding capacity can be accurately determined by extrapolation to the ordinate or the second component, a straight line corresponding to a binding of somewhat lower affinity and much larger capacity.


Somatomedin in cord blood: relationship to gestational age and birth size. Somatomedin (SM) was determined by bioassay in cord blood from 100 neonates born at 24-42 weeks of gestation and from three infants with major congenital malformations. SM levels rose with gestational age and had a positive correlation with birth weight, length and head circumference independantly of gestational age. These findings suggest a relationship between somatomedin and fetal growth.


Schistoma mansoni soluble egg antigens: determination of the stage and species specificity of their serologic reactivity by radioimmunoassay. Three highly purified Schistosoma mansoni egg antigens reactivity with sera from mice with chronic schistosomiasis mansoni (major serologic antigens-MSA1, MSA2, and MSA3) were utilized in radioimmunoassays for determining their stage and species specificity. Inhibition studies revealed that MSA1 was completely stage specific, since its binding to S. mansoni chronic infection serum (CIS) could not be inhibited either with cercarial or adult worm antigen. MAS2 and MSA3 were specific with regard to adult worm antigen but their binding to CIS was slightly inhibited by cercarial antigen. Immature eggs in comparison with mature eggs contained only negligible amounts of MSA1 whereas MSA2 and MSA3 were present in large quantities. Fluid from eggs hatched in spring water (hatch fluid-HF) contained considerable amounts of MSA1 as well as MSA2 and MSA3. With regard to species specificity, MSA1 essentially did not cross-react with crude soluble egg antigen (SEA) from Schistosoma japonicum and Schistosoma haematobium whereas MSA2 and MSA3 showed partial cross-reactivity. Antibody dilution studies with sera from animals and humans infected with heterologous schistosome species (i.e., S. japonicum and S. haematobium) indirectly confirmed the high degree of species specificity of MSA1. The degree of serologic specificity of MSA1 as demonstrated in this study parallels that of the sensitizing activity of S. mansoni eggs and SEA for granuloma formation, as demonstrated in previous investigations. This study, therefore, indicates that MSA1 may be a major immunopathologically active egg antigen. In addition, the high degree of species specificity of MSA1 suggests its use in the serodiagnosis of schistosomiasis mansoni.


The in vitro permeability of skin and buccal mucosa to selected drugs and tritiated water. The permeability of whole human skin, human dermis, whole pig skin, and canine buccal mucosa have been determined for four chemically different solutes: tritiated water, amphetamine, estradiol, and ouabain. Several new in vitro techniques for isolation, preservation, and permeability determination of these membranous tissues are described. Water permeabilities of human epidermis and dermis using these techniques agree well with published results. Human and porcine skins are very similar with respect to water permeability, while buccal mucosa is similar to dermis in its permeability characteristics to the four representative test agents. The permeability of hydrated whole skin is determined by the permeability of the epidermis, and the dermis and buccal mucosa behave as if they are water barriers exhibiting a permeability of about 30% of the diffusion through pure water, a difference that can be ascribed to the porosity and/or tortuosity of the tissue matrix.


Major proteins of soybean seeds. A straightforward fractionation and their characterization.


Nitrosopyrrolidine formation in fried bacon.


Automated determination of tryptophan in legumes and cereals.


Natural occurrence of alternariols in discolored pecans.


Heat-induced complex formation between myosin and soybean 7S globulins.


Leptospirosis australis--a case report.

Leptospirosis australis--a case report.


Plasma concentration of androstenedione during the bovine oestrous cycle. A radioimmunoassay with Sephadex chromatography for androstenedione is described. Concentrations of androstenedione in bovine peripheral blood during the oestrous cycle ranged from 80 to 100 pg/ml. There was considerable variation and no pattern suggestive of physiological significance emerged, unlike those of oestradiol and testosterone.


Changes in uterine and ovarian blood flow during the oestrous cycle in rats. The rates of uterine and ovarian blood flow during the oestrous cycle in rats were measured using radioactive microspheres. Blood flow was highest in the ovaries and uteri during pro-oestrus and lowest during metoestrus. During pro-oestrus, mean ovarian blood flow was 676-2 +/- 183-6 (S.D.) ml/min/100 g wet tissue and mean uterine blood flow was 249-7 +/- 120-1 ml/min/100 g. During metoestrus mean ovarian blood flow was 117-4 +/- 19-8 ml/min/100 g and mean uterine blood flow was 38-5 +/- 7-4 ml/min/100 g. In ovariectomized rats, uterine blood flow was 28-7 +/- 10-5 ml/min 100 g.


Variables affecting establishment of schedule-induced attack on pictorial targets in White King pigeons. White King pigeons exposed to food schedules before introduction of a colored photograph of a pigeon showed sustained schedule-induced attack on that image; additional birds given an early introduction to both the photograph and the schedule subsequently attacked the image at lower rates. Other pigeons attacked a second photograph of a pigeon regardless of whether it was introduced early or late. The late-introduction procedure was also effective in establishing attack on a projected image of a conspecific. The combined results showed that 14 of 17 White King pigeons given a late introduction to a pictorial target exhibited sustained attack against it and that a pigeon's initial reaction to a photograph of a conspecific when introduced early was a good predictor of subsequent schedule-induced attack on it.


Developmental aspects of secondary palate formation. Research on development of the secondary palate has, in the past, dealt primarily with morphological aspects of shelf elevation and fusion. The many factors thought to be involved in palatal elevation, such as fetal neuromuscular activity and growth of the cranial base and mandible, as well as production of extracellular matrix and contractile elements in the palate, are mostly based on gross, light microscopic, morphometric or histochemical observations. Recently, more biochemical procedures have been utilized to described palatal shelf elevation. Although these studies strongly suggest that palatal extracellular matrix plays a major role in shelf movement, interpretation of these data remains difficult owing to the complexity of tissue interactions involved in craniofacial development. Shelf elevation does not appear to involve a single motive factor, but rather a coordinated interaction of all of the abovementioned developmental events. Further analysis of mechanisms of shelf elevation requires development of new, and refinement of existing, in vitro procedures. A system that enables one to examine shelf elevation in vitro would allow more meaningful analysis of the relative importance of the various components in shelf movement. Much more is known about fusion of the palatal shelves, owing in large part to in vitro studies. Fusion of the apposing shelves, both in vivo and in vitro, is dependent upon adhesion and cell dealth of the midline epithelial cells. Adhesion betweeen apposing epithelial surfaces appears to involve epithelial cell surface macromolecules. Further analysis of palatal epithelial adhesion should be directed towards characterization of those cell surface components responsible for this adhesive interaction. Midline epithelial cells cease DNA synthesis 24-36 h before shelf elevation and contact, become active in the synthesis of cell surface glycoproteins, and subsequently manifest morphological signs of necrosis. Death of the midline epithelial cells is thought to involve a programmed, lysosomal-mediated autolysis...


Biosynthesis of DNA, RNA and proteins by mouse embryos cultured in the presence of a teratogenic dose of chlorambucil. The effect of chlorambucil on the rates of DNA, RNA, and protein synthesis in mouse embryos was investigated using a system of whole embryo culture. Embryos were isolated on the 11th day of gestation (33 +/- 3 somites) and grown in culture media for periods of 4-8 h. Reichert's membrane and most of the placental tissue was removed leaving only the amnion and visceral yolk-sac surrounding the embryo. In the presence of teratogenic doses of chlorabucil (15 mug/ml) the rate of DNA synthesis was significantly decreased at 4 and 8 h. RNA and protein synthesis were not inhibited at either of these times. A trend toward decreasing rates of protein synthesis at some time beyond 8 h was noted, but not tested.


Postimplantation development of blastomeres isolated from 4- and 8-cell mouse eggs. Blastomeres isolated from 4- and 8-cell mouse eggs were inserted into empty zonae and transferred to the oviduct. The products of both types of blastomere were capable of inducing decidual formation. One implant produced by an isolated blastomere from a 4-cell egg contained a small, retarded embryo at 5 1/2 days but most decidua from blastomeres of either 4- or 8-cell eggs contained only a few trophoblast giant cells. It is suggested that this lack of totipotency is due to insufficient cells being present at cavitation rather than restriction in developmental potential.


The permeability to cytochalasin B of the new unpigmented surface in the first cleavage furrow of the newt's egg. Two of 10 mug/ml cytochalasin B (CB) caused retraction of the first cleavage furrow in Triturus eggs, a spreading of the unpigmented surface from the furrow region and a flattening of the whole egg. CB appears to act against the contractility of the microfilamentous band at mid-cleavage so as to relax the furrow and also to weaken unpigmented surface to allow the egg to flatten. Uncleaved eggs and the initial formation of the cleavage groove were unaffected by CB. A fully-retracted first cleavage furrow reformed itself on transfer of the egg to normal medium but only at the time of second cleavage. Initiation of second cleavage depended upon there being sufficient of the original pigmented surface on the animal hemisphere. Tritium-labelled CB of high specific activty was prepared and used to study its ability to penetrate the surface of newt eggs during cleavage. Scintillation couting of whole eggs showed that CB was not taken into the newt egg until mid-cleavage (about 17 min after the double stripe stage) when new surface began to spread in the cleavage furrow. Fixation in glutaraldehyde and osmium tetroxide retained radioactivity in the egg, but more CB was retained after fixation in osmium tetroxide alone than after double fixation. Most of the retained radioactivity was in yolk platelets. Autoradiographs were prepared to sectioned eggs which had been fixed at late cleavage after [3H]CB had flattend the furrow. These showed that CB entered the egg through the unpigmented surface which formed in the furrow but it could not enter through the pigmented surface. The impermeability of the pigmented surface explains the observations that CB does not prevent initial furrowing at cleavage. Once inside the egg CB is transported slowly. CB penetrates to a limited extent beneath the pigmented surface from its border with the unpigmented surface in the first cleavage furrow and this seems insufficient in some circumstances to suppress the contractile phase of second cleavage.


The developmental analysis of an embryonic lethal (C6H) in the mouse. A development study of the effects of the C6H allele at the albino locus has identified the C6H homozygote as an early postimplantation lethal. Homozygous C6H embryos can first be recognized at 6 1/2-7 days of gestation by abnormalities of the ectoplacental and parietal endodern. At 7 1/2 days, mutant embryos appear severely retarded with obvious abnormalities in all germ layers. All C6H homozygotes are dead and resorbed by 8 days of development. It is proposed that the mutation interferes with the normal differentiation of the parietal endoderm, ectoplacental cone and extra-embryonic ectoderm of the egg cyclinder.


Experiments on blocking and unblocking of first meiotic metaphase in eggs of the parthenogenetic stick insect Carausius morosus Br. (Phasmida, Insecta). The eggs of the parthenogenetic stick insect Carausius morosus, which remain arrested in first meiotic metaphase until oviposition, must be activated in order to develop. The activating agent is oxygen from the air, which enters the egg cell through the micropyle. An exposure shorter than one minute is sufficient to release the blockage. In non-activated (micropyle-less) eggs the first metaphase chromsomes either degenerate or change into an interphase nucleus. This nucleus polyploidizes by endoreduplication, and then either degenerates or multiplies by amitosis. Similarly more generations of nuclei may arise resulting in a chaotic development. These nuclei survive better in the anterior region of the egg. The question of whether the cytoplasmic factors which control nuclear behaviour, also operate in eggs of C. morosus is discussed.


Protein synthesis and germ plasm in cleavage embryos of Xenopus laevis. (3H) leucine was injected into unfertilized eggs, fertilized eggs, and Stage 2-12 embryos of X. laevis. Incorporation of the leucine into protein by blastomeres containing germ plasm was studied autoradiographically. Eggs, both fertilized and unfertilized, actively synthesized protein, ad did embryos from Stage 2 onwards. Probably all blastomerers containing germ plasm were labelled. In embryos from Stages 4-12, the germ plasm itself was also labelled, and this result suggests that the germ plasm is metabolically active during cleavage.


Social experience and territorial aggression in rats: a replication with selected aggressive males.


Changes in the striatal adenylate cyclase activity following acute and chronic morphine treatment and during withdrawal.


Structure and function of the glandular vas deferens in Ascaris suum (Nematoda). The glandular vas deferens in the linearly arranged male reproductive tract in Ascaris suum produces substances which cause marked morphological and physiological changes in the spermatozoa. The glandular secretions, presumably formed by the rough endoplasmic reticulum and Golgi saccules, are extruded from the cells and coalesce to form homogeneous masses in the gland lumen. In sexually inactive worms the secretory material is separated from the spermatozoa by a sphincter comprised of neuro-muscular-like cells. During copulation the sphincter lumen enlarges and the spermatozoa and sperm-activating glandular material are mixed and simultaneously transferred to the female worm.


Thelazia lacrymalis in horses in Kentucky and observations on the face fly (Musca autumnalis) as a probable intermediate host. Eyes from 114 (30.3%) of 376 dead horses, examined from 3 April 1975 to 3 April 1976, were naturally infected with adult Thelazia lacrymalis; 1 horse was also infected with 1 male Thelazia skrijabini. Adult T. lacrymalis from dead horses were successfully transferred mechanically to the eyes of 3 of 4 Shetland ponies raised helminth-free. Larvae from gravid female T. lacrymalis underwent development in experimentally infected, laboratory-raised face flies (Musca autumnalis) and third-stage larvae ranging from 1.82 to 2.94 mm in total length were recovered at 12 to 15 days postexposure. A total of 866 naturally occurring face flies were collected from the head region of horses. Twelve of the face flies harbored larval stages of Thelazia spp. One of the larvae resembled third-stage T. lacrymalis that were recovered from the experimentally infected, laboratory-raised face flies. Introduction of 3 third-stage larvae from 1 face fly onto the cornea of a pony raised helminth-free resulted in the recovery of 1 male T. skrjabini 242 days later. In addition to the eyeworm larvae, other parasites recovered from the face flies included Heterotylenchus autumnalis, hypopi of astigmatid mites and a first instar beetle (Coleoptera: Rhipiphoridae). Data from these investigations indicate the likelihood that face flies are an intermediate host for T. lacrymalis and probably other species of Thelazia in this part of the country.


Changes in leadership appraisal as a function of the stress of a simulated panic situation. Research by Mintz and Kelley, Condry, Dahke, and Hill left unresolved the question of what level of personal threat leads to group incoordination of "panic behavior." The present study set out to resolve this issue and to explore the additional relationship between leadership and behavior in the panic situation. The dependent variables were Likert-type questionnaire items designed to investigate the level of responsibility attributed to a leader by members of a group as a function of four variables: (a) two levels of stress (threat of shock or of small monetary loss); (b) two levels of leadership authority (elected or appointed); (c) two conditions of leadership ("me-last" or "me-first"); and (d) group success or failure. The specific questions were adapted from earlier pilot work by Sulzer and Sisti. One hundred and forty-four males were run in this 2 X 2 X 2 X 2 factorial design with a nonfactorial control group. The task setting, which required subjects to retrieve their wooden cones through the same hole, was designed to be analogous to the kind of situation that would occur in a theater fire where only one narrow exit existed. The results support the contention of Kelley that group incoordination (panic) increases under personal threat. Additional results were: (a) Leaders facilitated achieving the goal of safe exit; (b) elected leaders were given more responsibility and were seen as more competent than appointed leaders, but only when the stress is comparatively low, as otherwise the difference in evaluation narrows and reverses; and (c) success or failure seems to have had little effect on the leader's evaluation by the group.


Diurnal variation and individual differences in the perception of intractable pain.


Psychophysiological aspects of the menstrual cycle. After a survey of literature on electrolyte changes associated with the varying excretion of hormones during the menstrual cycle, a study of 30 women aged 18-33 is reported.  Measurements of sodium and potassium ions in the saliva were made at 4 points in the menstrual cycle and, since previous work had shown bilateral asymmetry in sodium reabsorption in the eccrine sweat glands, samples were collected from both the right and left sides of the mouth.  The smallest sodium/potassium (Na+/K+) ratios were found at ovulation and the premenstruum.  This fits 2 sets of facts:  1) during stress Na+/K+ ratios decrease and 2) this decrease comes exactly when most women report feelings of irritability, anxiety, and such.   Differences in Na+/K+ ratios over points in the cycle were significant at p less than .001.  Differences between right and left side were significant during the premenstruum (p less than .05).  K+ was highest at ovulation (p less than .001) and the left side produced higher values (p less than .05).  Na+ was lowest at ovulation, highest at menstruation (p less than .001) with concentration on right side higher at menstruation (p less than .05). This seems to indicate that the right side not only reabsorbs Na+ more efficiently but it can also excrete more efficiently and maintains homeostasis more effectively.  Estrogen seems to play a major role in initiating these variations in body electrolytes, which are similar to stress reactions.  It is also suggested that salivary electrolytes, recorded for parotid saliva, reflect readings similar to that of plasma with Na+ and K+ tending to move in opposite directions.


Bio-feedback: opening discussant's remarks after Professor Neal Miller's talk.


Physiological responsivity of normal and sexually dysfunctional women during erotic stimulus exposure.


Eosinophil-mediated destruction of Schistosoma mansoni eggs.


The de Lange syndrome in one of twins.

The de Lange syndrome in one of twins. A pair of female monozygotic twins, one of them affected by the de Lange syndrome is described for the first time. Monozygosity was established by most of the accepted standards in use at the present time. Speculation is offered as to whether the discordance in the manifestation of the syndrome provides any clues for understanding its controversial pathogenesis. In this regard two genetic mechanisms are discussed. One is the hypothesis of a chromosomal or mitotic instability. The other possibility would be a postzygotic new mutation of a gene or large effect.


Clinical details, cytogenic studies,and cellular physiology of a 69, XXX fetus, with comments on the biological effect of triploidy in man. A triploid fetus, 69, XXX, aborted spontaneously at 26 weeks' gestation. It had multiple abnormalities including syndactyly of the hands and feet single palmar creases, hypoplasia of the adrenals and ovaries, hypertrophy of thigh muscles, and abnormalities of the brain. The placenta was large and showed hydatidiform degeneration. The pregnancy had been complicated by acute dyspnoea, pre-eclampsia, and postpartum haemorrhage. Detailed cytogenetic studies, using banding and fluorescence techniques, were performed on fetus and parents. Meiotic studies were made on the fetal ovaries. Muscle cell differentiation and electrophysiological relationships of cultured skin fibriblasts were examined in an attempt to study the way in which the extra haploid set of chromosomes exerts its effect on the phenotype. The antenatal diagnosis of late triploidy is discussed. The finding that 25 per cent of late triploids have spina bifida is further evidence that meningomyelocele has a genetic component and strongly suggests that this results from chromosomal imbalance or a regulatory gene disturbance.


Trimethylhydrazine hydrochloride as a tumor inducer in Swiss mice. A 0.05% solution of trimethylhydrazine hydrochloride (TMH) administered for a lifetime in drinking water to outbred Swiss albino mice, beginning at 6 weeks of age, induced tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in untreated controls were 5,22 and 0%, whereas in the treated groups the corresponding tumor incidences increased to 85, 44, and 6%, respectively. Histopathologically, tumors were classified as angiosarcomas of blood vessels and adenomas of the lungs and kidneys. The study thus demonstrated the tumorigenicity of TMH. Contrary to expectation, the chemical structure modification apparently failed to alter qualitatively the tumorigenic response.


Age incidence and site distribution of mammary dysplasias in young beagle bitches. The age incidence and site distribution of 2,142 mammary dysplasias were documented for 39 beagle bitches 6 months to 4 years of age. Lesion onset was at 2-3 years of age, at which time more than 50% of the females had dysplasias. Dysplasias appeared before palpable tumors. Posterior mammae developed more lesions than did anterior mammae. Thus the gradient for early onset of lesions coincided with the gradient for tumor frequency reported previously; a preneoplastic potential is suggested for (some) dysplasias. Problems of defining normal tissue are discussed.


Hepatic angiosarcomas in dogs: an excessive frequency as compared with man. A series of 18 angiosarcomas of the liver in dogs reported by veterinary schools in the United States and Canada suggested that certain breeds may have an excess of the tumor and that there is no marked predilection by sex. Histologic characteristics of hepatic angiosarcomas were similar in man and dog, but the relative frequency in dogs was about 25-100 times that of man.


Mutant lines of guinea pig L2C leukemia. II. Comparative cytogenetic studies and banding analyses of normal and leukemic karyotypes. Chromosomes of normal guinea pig (strain 2) cells and of cell lines dervied from a spontaneously arising leukemia were analyzed in detail. All cell lines studied, LG-L2C, GH-L2-C, BZ-LC, and EN-L2C, contained one M1 marker and two X chromosomes, in addition to other chromosome abnormalities specific for each cell line. The presence of the M1 marker and the two X chromosomes confirmed that all of these leukemic cell lines are derived from one ancestral line. Comparison of the chromosome markers and immunologic characteristics of these lines revealed that possibly the gene involved in the determination of C3 receptor sites is located on the terminal portion of the long arm of chromosome No. 2, but no other correlations could be made.


Tumorigenicity of tetramethylhydrazine hydrochloride in Swiss mice. Tetramethylhydrazine hydrochloride (TEMH) was administered in drinking water as a 0.125% solution to randomly bred Swiss mice for life beginning at 6 weeks of age. As a result of treatment, the incidence of blood vessel tumors rose from 5 to 96% in females and from 6 to 88% in males, while that of lung tumors increased from 21 to 36% in females and from 23 to 28% in males, as compared with untreated controls. The increased incidence of blood vessel tumors, but not of lung neoplasms, was statistically significant. Histopathologically, the tumors exhibited the characteristics of angiomas and angiosarcomas of blood vessels and adenomas of the lung. The investigation proved for the first time the tumorigenicity of TEMH. The possible role of increased methyl substitution on hydrazine in tumorigenesis was also discussed, as well as hydrazine derivatives as a tumor-producing class.


The psychiatric assessment of candidates for cosmetic surgery.


The accessory fibers of the sperm tail. High-sulfur and low-sulfur components in mammals and cephalopods.


The influence of vesical distension on the urethral resistance to flow: a possible role for prostaglandins? The possible role of prostaglandins in the mediation and/or modulation of the urethral response to vesical distension was investigated in female dogs. Three criteria for the possible involvement of these mediators have been investigated. Indomethacin could block the reduction of urethral resistance observed during vesical distension. Intra-arterial infusion of exogenous prostaglandin E2 resulted in a dose-dependent reduction in the urethral resistance to flow. Moreover, a significant release of prostaglandin E2 in the venous blood during the course of vesical distension could be demonstrated. The functional significance, mechanisms of release and mode of action of these highly active lipids are discussed.


Colpocystourethropexy: the way we do it. In pure stress urinary incontinence the sphincteric mechanism is intact. Restoration of normal position and support to the vesicourethral segment usually re-establish normal sphincteric function. A suprapublic approach is used to gain adequate mobilization of the anteriorr vaginal wall and vesicourethral segment. Full thickness sutures applied in the anterior vaginal wall as far lateral from the urethra as possible are then tied to Cooper's ligament. Forward and upward lifting of the vesicourethral segment is achieved but the urethra is free in a wide retropubic space. Normal position with limited mobility of the sphincteric segment is attained, yet compression or obstruction of the urethra and surgical trauma to the delicate sphincteric musculature are avoided. Adsorbable sutures are used. Permanent fixation is to be achieved by the postoperative fibrosis made possible after all retropubic fat has been cleared away. This technique has been uniformly successful in virginal cases and in the great majority of the least favorable cases, after repeated failures. Adequate mobilization proper placement of sutures and prevention of compression and surgical damage are the keys to longlasting successful repair.


Vesicoureteral reflux in identical twins.


Mediastinal choriocarcinoma in a chromatin-positive boy. A case of primary mediastinal choriocarcinoma in a chromatin-positive boy is reported. The incidence of neoplasms in patients with so-called Klinefelter's syndrome is discussed as well as embryogenesis and diagnostic evaluation in patients presenting with this tumor.


Theoretical and therapeutic potential of indoleamine precursors (2).


Trisomy 5 in two abortuses.

Trisomy 5 in two abortuses.


Tricho-rhino-phalangeal syndrome: report on three unrelated families.


A rare variant type of 6-phosphogluconate dehydrogenase found in Japanese.


Further examples of Gc variant (Gc J) found in a Japanese family.


Effects of rubidium on behavioral responses to methamphetamine and tetrabenazine. Different groups of mice were injected subcutaneously every other day with rubidium chloride at three doses (0.41(50), 1.23(150) and 3.69(450) meq/kg (mg/kg)) or with saline as a control for a period of 2-3 weeks. Rubidium administered acutely did not affect spontaneous locomotor activities, while it tended to increase the activities when administered repeatedly though the increase was not statistically significant. The methamphetamine-induced hyperlocomotor activities were potentiated in the rubidium groups as compared with those in the saline group, this effect of ribidium being increased with prolongation of repeated administrations. Monotonic decreases in ambulation after tetrabenazine were not significantly affected in the rubidium-treated animals though the decreases were sometimes preceded by slight increases and recovery from the decrement tended to be more rapid. After tetrabenazine in the rubidium-treated groups, incidences of catalepsy were increased and jumping behavior and Straub tail responses occurred in a few cases. The results suggest that rubidium potentiates the excitatory action of methamphetamine on spontaneous locomotor activities, as contrasted with inhibitory influence of lithium.


A transport mechanism of methyl mercury to egg albumen in layer Japanese quail.


Comparison of pathogenicity in chickens of Mycoplasma synoviae with special reference of a Japanese isolate.


Serological investigation on Salmonella carrier-dogs.


Histopathology of purulent arthritis of chickens.


Further investigation on the dye and hemagglutination tests for the latent swine toxoplasmosis.


Neonatal respirator allowing simultaneous ventilation and suction. A new type of respirator for newborns allowing tracheal suction and ventilation simultaneously is presented. Additional characteristics are: a partly disposable air supply system, no apparatus deadspace and with one exception no moving parts. The performance of the respirator under varied conditions of lung mechanics was tested using a pneumatic lung thorax analogue. The procedure of tracheal suction was simulated and the effect on tidal volume and alveolar pressure investigated. Triggervolume and response time were also determined. Analysis shows that the respirator has qualities of flow- and pressure preset ventilators. Tracheal suction during ventilation does not impair the delivery of tidal volume. In mechanical ventilation with PEEP the alveolar pressure remains positive throughout the respiratory cycle despite suction.


[Effectiveness of thyrocalcitonin in the treatment of steroid-induced osteoporosis].


Investigating ethnic prejudice among boys in residential treatment.


Cytoskeletal elements of chick embryo fibroblasts revealed by detergent extraction. Treatment of chick embryo fibroblasts with 0.5% Triton X-100 extracts most of the cell protein, leaving an organized part of the cell structure attached to the tissue culture dish. This "Triton cytoskeleton" consists largely of intermediate-sized filaments and bundles of microfilaments. SDS polyacrylamide gel electrophoresis reveals that this cytoskeleton is made up of three main proteins. One protein component is 42,000 daltons and co-migrates with muscle actin. The other two components are 52,000 and 230,000 daltons and remain quantitatively associated with the cytoskeleton during the detergent extraction. The possible identity of these three protein components and their organization into a supramolecular structure is discussed.


Morphological and biochemical abnormalities in hearts of cardiac mutant salamanders (Ambystoma mexicanum). The effect of homozygosity for recessive gene c in Ambystoma mexicanum is the absence of a heartbeat even though initially heart development appears normal. Mutant embryos (c/c) are first distinguishable from their normal siblings (+/+;+/c) at stage 34 (7 days after fertilization) when the normals develop contracting hearts. The mutant hearts at this stage, upon gross examination, appear structurally normal but fail to beat. Nevertheless, the mutants survive through stage 41, which is about 20 days beyond the heartbeat stage, and they exhibit normal swimming movements, indicating that gene c does not affect skeletal muscle. Electron microscopic studies of normal hearts show some myofibrils to be present at stage 34; by stage 41, the normal myocardial cells have become highly differentiated muscle cells. Although some mutant heart cells contain a few thin 60 A and thick 150 A filaments, organized myofibrils are absent. Instead, amorphous proteinaceous collections are prominent. Heavy meromyosin (HMM) binding experiments were performed on mutant hearts to determine whether the myocardial cells contain actin. Mutant myocardial cells that are glycerinated but not treated with HMM contain intact amorphous bodies. After incubation in HMM, the amorphous collections are no longer present and large numbers of decorated actin filaments appear. The.results suggest that the amorphous proteinaceous collections contain actin in a nonfilamentous form, and the addition of HMM induces this actin to polymerize into filaments. SDS-polyacrylamide gel electrophoresis of mutant heart tissue supports this conclusion by showing a prominent 43,000 dalton band suggestive of actin. The electrophoresis experiments also demonstrate a significant reduction of myosin heavy chain (200,000 daltons) in mutant hearts when compared to normal, and this latter observation is confirmed by radioimmunoassay experiments. Muscle tropomyosin (34,000 daltons), prominent in normal hearts, is virtually nonexistent in mutants. Thus, it appears that this single gene mutation affects the accumulation and organization of several different muscle proteins, including actin, myosin, and tropomyosin.


Selective breeding of rats for differences in reactivity to alcohol. An approach to an animal model of alcoholism. I. General procedures. Strains of rats are being developed which have distinct responses in spontaneous locomotor activity to a subhypnotic dose of alcohol. The purpose is to produce one strain in which the injection of a standard dose of alcohol will result in objectively measurable intoxication and a second in which an identical dose will result in virtually no effect.


Effect of housing density on alcohol consumption by rats. Rats housed six to a cage drank significantly more of a 10% alcohol solution than those housed three per cage or individually. Open-field behavior was negatively correlated with alcohol intake.


Alcohol withdrawal effects on brain serotonin in mice behaviorally attracted to alcohol. Serotonin concentration in whole brain tissue of CF1 mice behaviorally attracted to a 3% alcohol solution was significantly depressed 48 hours after access to the solution was denied. Norepinephrine concentration was not affected.


Studies on the mechanisms of 6-hydroxydopamine cytotoxicity. The uptake-accumulation and binding of radioactivity in mouse heart after administration of the catecholamine neurotoxin [3H]6-hydroxydopamine (6-OH-DA, 1 or 3 mg/kg, i.v.) has been investigated. It was confirmed that a substantial portion (8--20%) of the radioactivity taken up and retained by the heart could not be extracted with perchloric acid, in all probability representing covalently bound oxidation products of 6-OH-DA to tissue proteins. Pharmacological analysis showed that a large part of this fraction was associated with the adrenergic nerves. The time-course of the perchloric acid resistant binding to the adrenergic nerves was found to parallel that of the neurotoxic action of 6-hydroxydopamine as evaluated by monitoring the change in [3H]noradrenaline uptake. Calculation of the intranelronal 6-hydroxydopamine concentration (average) needed to induce degeneration showed it to be in the order of 50 mM. The binding ratio for tritium deriving from [3H]6-OH-DA between the intraneuronal and extraneuronal compartments was found to be 10,000 to 30,000, pointing to a very high neuronal specificity for 6-hydroxydopamine. The 'covalent' binding of oxidation products of [3H]6-OH-DA was considerably reduced after desipramine or 1-phenyl-3(2-thiazolyl)-2-thiourea administration, treatments both known to protect the adrenergic nerves from undergoing degeneration. Conversely it was found that the binding increased during conditions known to potentiate the neurotoxic action of 6-hydroxydopamine, e.g., after monoamine oxidase inhibition with nialamide. Subcellular fractionation studies indicated that the predominant site of interaction between 6-hydroxydopamine oxidation products and neuronal proteins is the cytoplasm and the axonal membrane. Analysis of the effect in vivo administration of 6-hydroxydopamine on the field-stimulated induced release of [3H]noradrenaline previously taken up in the adrenergic nerves showed a 6-hydroxydopamine indiced reduction in [3H]noradrenaline release which was approximately proportional to the reduction in the number of nerve terminals. These findings further support the view that 6-hydroxydopamine acts largely in an "all-or-none' fashion with respect to the neurodegenerative action. Administration of [3H]dopamine also resulted in a fraction which was not extractable with perchloric acid, although this fraction was very small compared to that found after an equal dose of [3H]6-hydroxydopamine. These data may indicate that oxidation products of dopamine can interact with tissue proteins. From the present results it can be concluded that there is a close relationship between 'covalent' binding of 6-hydroxydopamine oxidation products to neuronal elements and the cytotoxic action of 6-hydroxydopamine, indicating that this binding may play an important role in the neurodegenerative action of 6-hydroxydopamine on catecholamine neurons.


The interaction between spontaneous convulsions and tolerance to hexobarbital in the abstinence after chronic barbital treatments in the rat.


Neonatal corticoid administration: retardation of adrenal rhythmicity and desynchronization of puberty.


Cultivation of mammalian cell lines in serum-free chemically defined medium.


Improved synthetic media suitable for tissue cllture of various mammalian cells.


Long-term preservation of the Ehrlich ascites tumor.


Isolation of drug-resistant clones of Ehrlich ascites tumor cells.


Diabetic retinopathy.

Diabetic retinopathy.


Bone-resorbing activity of analogues of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol: effects of side chain modification and stereoisomerization on responses of fetal rat bones in vitro.


Induction and decay of aryl hydrocarbon hydroxylase activity in mouse 3T3 cells.


Oxygen-dependent reaction of 6-hydroxydopamine, 5,6-dihydroxytryptamine, and related compounds with proteins in vitro: a model for cytotoxicity.


Stabilization of double-stranded DNA molecule by non-histone peptidic effector from calf thymus. A peptidic effector from calf thymus causes a strong stabilization of DNA double-stranded molecule in vitro. The active factor was isolated from aqueous ultrafiltered thymus extracts and purified by means of chromatography on DEAE-cellulose and then on Dowex 50 WX2. The purified thymic factor was characterized as a peptide of low molecular weight (less than 5000). The biological activity of the thymic factor cannot be attributed to a histone fragment. Melting data of the control DNA and of the DNA-active factor complex in various conditions of ionic strength and dielectric constant of the solution medium are recorded.


'3H-testosterone distribution and binding in rat thymus cells in vivo'. Autoradiography and biochemical investigations showed that [3H]-testosterone where injected intraperitoneally into male white rats was incorporated rapidly into thymus lymphocytes. Thymic cortex contained more silver grains than medulla, and larger lymphocytes were more labelled than medium or small lymphocytes. Cytosol fraction of thymus cells labelled in vivo with [3H]-testosterone, contained the largest quantity of labelled hormone. A 4S cytosol fraction binds [3H]-testosterone. This could be separated by Sephadex chromatography or by linear sucrose gradient centrifugation. Nuclear extract contained also a small quantity of the labelled hormone.


Synthesis of delta crystallin from embryonic chick lens messenger ribonucleoprotein complex. A single, major 21 S messenger ribonucleoprotein (mRNP complex) was isolated and purified by sucrose gradient centrifugation after EDTA treatment of high salt washed polysomes from 15 day embryonic chick lenses. A 17 S mRNA was released from the 21 S subunit of delta crystallin. Similar results were obtained with the 17 S mRNA released from the 21 S mRNP complex.


A xeroderma pigmentosum patient having a high residual activity of unscheduled DNA synthesis after UV is assigned to complementation group A.


Characterization of poly(A)-protein complexes isolated from free and membrane-bound polyribosomes of Ehrlich ascites tumor cells. Proteins present in messenger ribonucleoprotein particles were labeled with [35S]-methionine in Ehrlich ascites tumor cells in which synthesis of new ribosomes was inhibited. Poly(A)-protein complexes were isolated from free and membrane-bound polyribosomes by sucrose gradient centrifugation and affinity chromatography on oligo(dT)-cellulose. Both classes of Poly(A)-protein particles contain a poly(A) chain of about 70 adenyl residues and a protein with a molecular weight of 76000 attached to it.


Cytoskeletal control of surface membrane mobility. Cytochalasin B induced redistribution of actin microfilaments into a bulge of the cytoplasm, bringing cell-surface elements to the corresponding surface area. This process was reversible, inhibited by colchicine and enhanced by antibodies to cell-surface antigens.


Growth regulation of cells grown in suspension culture.


Cell surface design.

Cell surface design.


Separation of clonogenic cells from stationary phase cultures and a murine fibrosarcoma by density-gradient centrifugation.


Digynic triploidy after superovulation in mice.


Mutagenesis and transformation of normal cells by chemical carcinogens.


Structure of porcine pancreatic prephospholipase A2.


A human chromosomal determinant for susceptibility to herpes simplex virus.


Uniqueness of plasminogen activators.

Uniqueness of plasminogen activators.


Effect of plant cytokinins on microfilaments and tight junction permeability.