The 3' terminal sequences of human alpha and beta globin messenger RNAs: comparison with rabbit globin messenger RNA. Sequences of 43 and 70 nucleotides adjacent to the 3' terminal poly(A) of human alpha and beta globin mRNAs have been established. Sequence analysis of complementary DNA from both normal and thalassemic globin mRNA preparations was carried out using endonuclease IV digestion and limited synthesis procedures. The two RNA sequences are 83% homologous to rabbit globin mRNA (Proudfoot, 1976), and a part of the alpha globin mRNA sequence codes for the carboxy terminus of human alpha globin Constant Spring (Clegg, Weatherall, and Milner, 1971). This latter result predicts that the 3' noncoding region of human alpha globin mRNA is exactly 112 nucleotides, while the 5' noncoding region is probably about 50 nucleotides.


Chromatin organization in nuclei of sea urchin embryos. Comparison with the chromatin organization of the sperm. The chromatin in sea urchin embryo nuclei and that in sperm heads are both organized in nucleosomes but show marked differences when analyzed by endonuclease digestion. Sperm chromatin DNA appears to be totally organized in nucleosomes that are highly resistant to nuclease hydrolysis. The kinetics of formation of acid-soluble oligonucleotides is slow and concerns only about 50% of the total DNA. In contrast, the DNA of embryo chromatin does not appear to be totally organized in nucleosomes since 5 to 10% is rapidly and preferentially hydrolysed into acid-soluble oligonucleotides without any appreciable fragmentation of the remaining parts. Futher digestion causes the formation of the usual pattern of DNA bands, as detected by gel electrophoresis. The length of the DNA segment associated with the embryo nucleosomes appears to be shorter than that of the DNA segment associated with the sperm nucleosomes. The kinetics of formation of acid-soluble oligonucleotides upon digestion of embryo chromatin is much faster than that of sperm chromatin and concerns almost all the chromatin DNA.


Studies on peptides. LXII. Synthesis of the protected octadecapeptide corresponding to positions 26 through 43 of porcine gastric inhibitory polypeptide (GIP).


Studies on peptides. LXIII Synthesis of the octacosapeptide corresponding to positions 1 through 28 of porcine gastric inhibiting polypeptide (GIP).


Studies on peptides. LXIV. Synthesis of the tritetracontapeptide corresponding to the entire amino acid sequence of porcine gastric inhibitory polypeptide (GIP).


Studies on peptides LXV. Conventional synthesis of a new hypothalamic peptide, bovine neurotensin.


Studies on peptides. LXVI. Synthesis of the protected heptadecepeptide amide related to the C-terminal portion of porcine cholecystokinin-pancreozymin (CCK-PZ).


Studies on peptides. LXVII. Synthesis of the hexadecapeptide corresponding to position 1 through 16 of porcine cholecystokinin-pancreozymin (CCK-PZ).


Studies on peptides. LXVIII. Synthesis of the tritriacontapeptide amide corresponding to the entire amino acid sequence of the desulfated form of porcine cholecystokinin-pancreozymin (CCK-PZ).


Vitamin A acid: clinical investigations with 405 patients. Vitamin A acid (retinoic acid) is less toxic than vitamin A and seems to be an important advance in dermatology. Its therapeutic effect was investigated in clinical studies involving 405 patients. Biochemical investigations have shown that the administration of vitamin A acid is associated with elevation of serum levels of retinol and carotene and after high dosage symptoms develop identical with hypervitaminosis A. Several possibilities regarding the mode of action of vitamin A acid are discussed.


Perioral dermatitis: etiology and treatment. Ninety-five patients with perioral dermatitis were studied from an epidemiological aspect. Consistent clearing of the eruption was obtained with oral tetracycline in combination with a topical sodium sulfacetamide-sulfur-hydro-cortisone lotion. Comparison of the study group of patients to a group of 50 control patients revealed highly significant quantitative differences in the cosmetic preparations used by the two groups. This latter finding would suggest that lubricating and moisturizing products play some part in the etiology of perioral dermatitis.


Malignant hemangioendothelioma (angiosarcoma).


Allergic rhinitis and the technique of immunotherapy.


Adverse drug reactions.

Adverse drug reactions.


Prognostic significance of ploidy level in human tumours. II extra-uterine cancers and summary of data on 1171 tumours. The 5-year survival rate of 78 patients with carcinoma of the ovary showed that the prognosis was significantly better when the tumour modal DNA value was in the diploid region than when it was near-triploid or above. Similar data on 140 patients with carcinoma of the breast and 52 with carcinoma of the bladder also suggested a better prognosis for the near-diploid tumours. Among 105 carcinomas of the large bowel, however, there were more survivors in the high-ploidy than in the near-diploid group, although the difference was not statistically significant. The varying relationship between ploidy and prognosis, depending on the site or histological type of the tumour, is briefly discussed on the basis of the 1171 cases included in the present and a previous paper.


The role of physical dependence in animal models of human alcoholism. This paper critically examines the concept that physical dependence is a necessary attribute for animal models of human alcoholism. On the basis of a review of the literature, it is argued that, since the production of physical dependence requires the presence of continuous high blood-alcohol levels, and since the production of preference for alcohol requires intermittent presentation of alcohol, the two cannot, in principle, be established in the same organism at the same time. It is further argued that physical dependence does not play a role in the development of high alcohol intake in animals. The implications of these observations for human alcoholism are discussed.


Sustained administration of cyclazocine for antagonism of morphine. The plasma levels, distribution and excretion of tritium were determined after administration of a single or sustained dose of 3H-cyclazocine to naive and morphine-addicted rats. The plasma levels reached and maintainat animals tolerant to morphine were cross-tolerant to cyclazocine. Although only half the administered radioactivity was excreted after either a single dose or a continuous administration, no appreciable concentration was found in any of the organs studied. The behavior of a single or sustained dose of cyclazocine was also determined in rabbits to evaluate the effect of the implant site on the drugs release rate and tissue biocompatibility. The release-rate of 3H-cyclazocine from a glyceride matrix implanted subcutaneously or intramuscularly could be controlled by modification of the matrix itself or by manipulation of the drug concentration within the matrix. Durations of action between a few days and a month were obtained by these means from devices that were both biodegradable and tissue compatible. The results indicate that the procedures used here may provide a practical means for administering narcotic antagonists to addicts.


Liberty caps: recreational hallucinogenic mushrooms.


Isolated perfused rabbit lung: a critical appraisal. The isolated perfused lung (IPL), when compared to available in vitro and in vivo pulmonary systems, is a preparation that fulfills a majority of the ideal criteria for studying metabolism, binding and/or physiological response to xenobiotics. The IPL is an exceptionally useful method when there is a need for concurrent administration of multiple agents in different physical forms. Various details such as physiological and biochemical parameters and the construction of a small animal tracheal valve system are discussed.


Survival of octogenarians: six years after initial chromosome examination. The frequencies of hypodiploidy, hyperdiploidy, monosomy C, monosomy G, and breaks were lower in the 19 female octogenarians who survived chromosome examination by six years than in the 19 who died, although none of the differences were statistically significant. In men, if anything, the trend was in the opposite direction with the nine survivors having higher frequencies than the 14 decedents. Again the differences were small and none were statistically significant. In neither sex, was there a relationship between length of survival and any of the parameters examined. Repeat chromosome examinations (two each, average interval 2.4 years) were available for seven women (one survivor and six decedents). There were no statistically significant differences between the two chromosome examinations except for an increase in monosomy C. Seven individuals, however, including but a single survivor, form too small a group to permit definitive conclusions about the lack of a relationship between chromosomal changes and survival.


A behavioral-chromosome relationship in the elderly: a critical review of a biobehavioral hypothesis. The evidence for the hypothesis that an increased frequency of hypodiploid cells is related to mental status in older persons, as well as the underlying assumptions crucial to the hypothesis, are reviewed. Results of chromosome examinations reported by several independent laboratories favor an increasing proportion of hypodiploid cells in older age groups as well as sex differences in the level and distribution of missing chromosomes. However, the presence, extent, and development course of chromosome loss associated with major modifying variables and their interactions, e.g., age, morbidity, sex, environmental conditions, remain to be empirically documented. Furthermore, the meaning of chromosome loss, including its relationship to mental status, is not clear.


Immunoglobulin levels and intellectual functioning in the aged. Significant positive correlations between vocabulary test scores and serum levels of immunoglobulins, IgG and IgM, were obtained for 14 subjects ranging in age from 83-100 years (mean 89.0 years). This positive association with vocabulary scores is a result contrary to data reported by other investigators. The interrelationship between measures of behavior, central nervous system and immunologic function deserve further attention.


Life span characteristics in the male Fischer rat. Survival data are reported for 572 male non-breeding Fischer rats, representing offspring from brother-sister matings, maintained at a constant temperature and humidity, exposed to twelve hours of artificial lighting and to twelve hours of darkness per day, and fed a standard laboratory diet ad libitum. The mean longevity for these male rats was 642 days and the median longevity was 659 days; the longest-lived individual survived to 1192 days. Animals surviving beyond the median life span for this colony were found to lose a greater percentage of body weight during the last few weeks before death than did shorter-lived animals. Offspring born of parents one year of age showed no significant difference in longevity from those of three-month old parents. Moreover, the longer any animal lived, the greater the maximan weight which he obtained.


The influence of rainfall on diet and reproduction in four African rodent species.


New combined oral contraceptive with incremental progestogen dosage regimen. In a study of 506 women, 272 took a total of 2124 cycles of combined preparations of norgestrel and 234 women took a total of 2002 cycles of a combined contraceptive with incremental progestogen doses, in which the total D-norgestrel was 1800 g as opposed to 5250 g in the combined preparation.  The step-up preparation group had a similar rate of side effects as the combined preparation group; however, women using the step-up preparation had significantly diminished intermenstrual bleeding after the 6th month of use.  The step-up regimen has not induced any cases of endometrial hyperplasia but does have an inhibiting effect on endometrial proliferation in the 1st half of the cycle.  The step-up preparation has similar effects on the hypothalamo-hypophysial-ovarian axis as the combined pill.  The step-up preparation appears to inhibit ovulation from the 1st cycle as indicated by the absence of LH and FSH midcycle peaks and the low 17 beta-estradiol levels in the 2nd half of the cycle; therefore, the step-up preparation should be classified as a new combined, not sequential, oral contraceptive.


Sexual behaviour of bulls at pasture: a review.


Influence of exogenous phosphorus on uterine fluids composition.


Development of malignant goiter by defatted soybean with iodine-free diet in rats. Hyperplastic goiters were observed frequently in female rats of Wistar strain when given defatted soybean under iodine deficiency for 6 to 12 months. The findings in the thyroid were those of malignant tumors in which the features of thyroid carcinomas were seen, accompanied with metastasis in the lungs of some animals. Enlargement of the thyroid was completely inhibited in rats when a small amount of iodine was added to the diet. The role of soybean factor(s) which causes enlargment of the thyroid is discussed in relation to the development of malignant goiter, together with pathological findings in the animals.


Estrous behavior and ovarian activity in peripuberal heifers. Estrous behavior and ovarian activity were investigated in peripuberal heifers.  Reproductive tracts of 37 Holstein heifers were examined per rectum twice weekly beginning at least 30 days before the 1st ovulation and continuing until 10 days after the 7th ovulation.  The signs of 1st estrus occurred at an average of 279 days of age and the 1st corpus luteum was not detected until 30 days later (p  .01).  The mean interestrual interval was 20 days for the 1st 7 cycles (p  .05).  The differences in interestrual intervals for cycles accompanied by silent, nonstanding, and standing estrous behavior, and by different ovarian conditions were not significant (p  .05).  Silent, nonstanding, and standing estrus occurred during 7, 25, and 68% of 245 estrous cycles, respectively.  The occurrence of standing estrus increased from the 1st to 7th cycle (p  .01).  Normal corpora lutea occurred during 61% of 245 cycles, cystic corpora lutea during 14%, anovulaton during 14%, and cystic follicles during 11%.  The occurrence of anovulation decreased from 1st to 7th estrus while the occurrence of corpora lutea increased during the same period (p  .01).


On the regularities of distribution of Hypoderma bovis De Geer larvae parasitizine cattle herds in different parts of the range of this warble fly. The type and parameters of the distribution of the second and third instar larvae of Hypoderma bovis in cattle herds in Czechoslovakia (54 herds, 7233 head), Mongolia (20 herds, 1809 head) and the USSR (48 herds, 4978 head) were studied. A statistical analysis showed a) that in the majority of cases negative binomial distribution serves as a model of the distribution of larvae with sufficient reliability; b) that the regularity of dependence of the distribution exponent k of the negative binomial distribution on the incidence of infestation remains constant in different parts of the range of thes warble fly. The latter fact indicates that the regulatory systems limiting the population numbers of this warble fly are associated with host-parasite relationships and do not depend on a complex of conditions specific for various natural zones. In order to understand the regulatory processes in parasite populations it is necessary to study equally the regulatory mechanisms operating primarily on the level of specimens as well as the regulatory systems operating on the level of populations.


Histopathological changes and the genesis of adiaspiromycomas in mice infected intraperitoneally with Emmonsia cresens Emmons et Jellison, 1960. Following an intraperitoneal inoculation with a suspension of aleuries of the funtus Emmonsia crescens, characteristic adiaspiromycomas originate in the abdominal cavity; a generalisation of the infection was caused by lymphogenic and haematogenic dissemination. At first, fragments of the mycelium became implanted and started to grow on the peritoneum; these were quickly destroyed by a gradually increasing leukocytic reaction. In the first month of infection nodules were formed mainly on predisposed sites in the abdominal cavity. Inside these nodules we found aleuries in the granulation tissue and a necrotic centre enclosing the accumulated inoculum. Development was delayed in aleuries released from agar particles after their resorption and in aleuries originating from remnants of the inoculum. This accounted for an initial heterogeneity of spherules in the nodules. The original nodules fus-d and formed large fibrous adiaspiromycomas. In the following months atypical spherules produced in large numbers by minute, developmentally retarded, budding spherules from the zone bordering the centres, were found inside these cel layer succumbed to regressive changes. The viability of these large spherules was confirmed by a finding of live adiaspores even at as late a time as 19 months after infection.


Monographs on fragrance raw materials.

Monographs on fragrance raw materials.


The inhibitory effect of hydrocortisone on the chicken embryo cartilage somatomedin assay. In a study of the effects of hydrocortisone on the embryonic chicken cartilage somatomedin assay, in the absence and in the presence of normal human reference serum (NHRS), it was found that: (1) The basal uptake of 35S into chicken embryo pelvic cartilage was reduced when hydrocortisone hemisuccinate was added to the incubation medium in concentrations ranging from 1.5 to 1.5 X 10(5) ng/ml. There was a correlation between the inhibitory effect and the quantity of hydrocortisone added (r=-0.869; p less than 0.01). (2) The 35S uptake stimulated by 1.25 and 5% serum present in the incubation medium was reduced by hydrocortisone in a final concentration range of 150-1.5 X 10(5) ng/ml incubation medium. The minimal dose was 1,000 times that required to affect the basal 35S uptake. (3) When hydrocortisone was directly added to the NHRS, its interfering effect on the 35S uptake stimulated by 1.25, 5 and 20% of serum in the incubation medium was demonstrable with 5 X 10(5) ng hydrocortisone/ml serum. This concentration exceeded the physiological level of hydrocortisone by a factor of 5,000.


Familial male internal pseudohermaphroditism; report on a case. A rare case of male internal pseudohermaphroditism is described. The patient had normal external male sexual characteristics but unilateral cryptorchidism. Three of his four brothers had also cryptorchidism and were also involuntary infertile. One of them was later operated and a uterus found intra-peritoneallu. The patient's parents were cousins and the possible importance of an inheritable defect is discussed. The patient's karyotype was normal.


Studies on the biosynthesis of cyclitols, XXXV. On the mechanism of action of myo-inositol-1-phosphate synthase from rat testicles. The animal myo-inositol-1-phosphate synthase is competitively inhibited by pyridoxal phosphate and trinitrobenzensulphonate, both compounds known to prevent Schiff's base formation. When incubated with labelled substrate and then treated with NaBH4, label can be recovered in the enzyme protein. In analogous experiments with tritiated NaBH4 the enzyme protein also becomes labelled; after hydrolysis of such protein only one labelled compound, derived from lysine and D-glucose 6-phosphate, could be isolated. Its exact structure is not yet known. From these results it can be concluded that during its action myo-inositol-1-phosphate synthase forms a Schiff's base with its substrate, in analogy to the class I aldolases.


Synergistic effect of estradiol benzoate and dihydrotestosterone on aggression in mice.


Postpartum aggression in mice: the influence of suckling stimulation.


Effects of androgen on scent marking and aggressive behavior of neonatally bulbectomized female Mongolian gerbils (Meriones unguiculatus).


The effect of a bacterial extract on synovial cells in tissue culture. The studies reported here were undertaken to determine if Erysipelothrix crude extract (CE) could elicit consistent, detectable alterations in synovial cells in vitro. Synovial cells of rabbits were cultured in vitro and data about normal synovial cells in vitro were presented. Such cells were consistently and characteristically affected by exposure to small amounts of CE; an effect that was neutralized in the presence of specific and anti-CE anti-serum. With an increase in the amount of CE added to the cells in culture, a decreasing number of cells was formed but protein content remained relatively constant.


Culture characteristics of cells derived from type II pneumocyte enriched fractions from rabbit and rat. Type II cell enriched fractions were isolated from rabbit and rat lungs using density gradient centrifugation. Cultures established from these fractions contained predominantly cells similar in most morphological respects to type II pneumocytes. These were in continuous replicating culture for 1 year and still exhibited contact inhibition. Membrane-bound structures reminiscent of, but no longer strictly identical to, type II cell lamellar cytosomes were seen in cells from these long-term cultures although their numbers were reduced in comparison to lamellar bodies in freshly isolated cells. Mitochondrial numbers and sizes, determined morphometrically, were reduced after culture in comparison to freshly isolated type II cells and those in situ. Phosphatidylcholine was synthesized by these cells and released into the extracellular medium. Application of laser activated electronic sizing data, confirmed by direct micrometry, demonstrated a significant increase in cell size as a function of culture. This sizing data, after prior confirmation by electron microscopy, was used as an aid in identifying type II cells and macrophages in dispersion, especially with those cells derived from rabbit lungs.


A clinico-pathological study of urinary tract malformations in perinatal deaths.


Diagnostic aspects of bladder angiography in urinary bladder tuberculosis. Histopathological and angiographic findings were correlated in 6 cases of tuberculosis of the urinary bladder. The number of vessels was only slightly increased in the initial and fibrotic stages, whereas hypervascularization was observed in the exudative and productive stages. Otherwise the angiographic changes were nonspecific. Thus it was not possible to distinguish tuberculous cystitis from cystitis of other genesis, and in some instances from tumours of the urinary bladder either.


Malignant testicular tumors in three  brothers. Three brothers out of four had malignant testicular tumors. The first of them had choriocarcinoma, the second seminoma, and the third teratocarcinoma of the testis.


Patterns of labor in native and immigrant population in Israel. The application of cervical dilatation rates as a predictive index of the outcome of labor was tested among various subgroups of the Israel population. Cervical dilatation rates, gestational ages, birth weights, initial fetal head station, cervical dilatation at head engagement, and incidence of delivery problems were similar among Jewish patients, both native born and foreign; and among Arab patients. Generally, primiparas entered labor with lower fetal head station and reached head engagement with less cervical dilatation than did multiparous or grand multiparous patients. The results suggest that the rate of cervical dilatation, as measured early in the active phase of labor, can be used with equal confidence among all our population groups to forecast type of delivery. Early in the active phase of labor, women in whom the probability of a spontaneous delivery is approximately 95% can be separated from those cases in which intervention will be necessary.


Cerebral distress in full-term newborns and its prognostic value. A follow-up study of 90 infants. The history of 90 full-term infants with neonatal cerebral distress was examined. Informations concerning pregnancy, delivery, neonatal status, clinical and laboratory evolution were compared with final outcome in each case. It was then possible to distinguish certain clinical features significantly associated with poor prognosis. After statistical analysis, different adverse criteria were selected, such as severe neonatal asphyxia, associated respiratory disorders, acute anemia, and especially neurological signs with regard to their chronology. This part of the study has resulted in a classification of the neurological signs and has permitted the description of both malignant and benign cerebral distress syndromes.


The ultrastructure of the fungus Trichoderma viride and investigation of its growth on cellulose.


Effect of temperature and added polyphosphate on the survival of salmonellae in poultry meat during cold storage.


Sulfate incorporation from ascorbate 2-sulfate into chondroitin sulfate by embryonic chick cartilage epiphyses. Radioactivity was significantly incorporated from ascorbate 2-[35S]sulfate into chondroitin sulfate by embryonic chick cartilage epiphyses. The extent of incorporation was comparable with that from inorganic [35S]sulfate. The radioactive chondroitin sulfate formed from ascorbate 2-[35S]sulfate gave two radioactive disaccharides on chondroitinase-ABC [EC 4.2.2.4] digestion. The incorporation was markedly decreased by inorganic sulfate. The time course of incorporation from ascorbate 2-[35S]sulfate and inorganic [35S]sulfate into chondroitin sulfate and the constituent disaccharides suggest that the incorporation rates from the two radioactive substances are different.


Studies on the hydrazinolysis of glycoproteins. Core structures of oligosaccharides obtained from Porcine thyroglobulin and pineapple stem bromelain. Hydrazinolysis of porcine thyroglobulin glycopeptides and of pineapple stem bromelain [EC 3.4.22.4] permitted the isolation of almost intact carbohydrate chains of these glycoproteins. On the basis of permethylation analyses of the released oligosaccharides after reduction with NaBH4, the core structures of Unit A-type and Unit B-type carbohydrate chains of porcine thyroglobulin were deduced to be Manalpha1 leads to 6[Manalpha1 leads to 3]Manbeta1 leads to 4GlcNAcbeta1 leads to 4[Ralpha1 leads to 6]GlcNAc leads to Asn (Unit A-type, R=H; Unit B-type, R=Fuc), and that of bromelain was found to be Manalpha1 leads to 6[R'1 leads to 2]Manbeta1 leads to 4GlcNAcbeta1 leads to 4[R1 leads to 3]GlcNAc leads to Asn (R'=Xylbeta and R=Fucalpha, or R'=Fucalpha and R=Xylbeta). From these results, it appears that the hydrazinolysis method is applicable to wide variety of glycoproteins which have an N-glycosylamine linkage between the carbohydrate and peptide moieties, regardless of the type of linkage to the most proximal N-acetylglucosamine residue which is bound to asparagine.


Bovine plasma HMW and LMW kininogens. Structural differences between heavy and light chains derived from the kinin-free proteins.


Isolation of two forms of activated C1s, a subcomponent of the first component of rabbit complement. Two forms of activated C1s, a subcomponent of the first component of complement, were present in preparations of C1 specifically purified from rabbit serum by affinity chromatography on IgG-Sepharose 6B and were separated by DEAE-cellulose chromatography in the presence of EDTA. These two activated C1s, designated C1s(I) and C1s(II), were indistinguishable with regard to hemolytic activity as well as C1s esterase activity, though they had different molecular weights. C1s(I) had a molecular weight of 106,000, consisting of H and L chains connected by disulfide bonds; the molecular weights of the chains were 70,000 and 36,000, respectively. On the other hand, C1s(II), with a molecular weight of 72,000, consisted of two chains each with a molecular weight of about 37,000, which were also connected by disulfide bonds. These results suggest that, in the case of rabbit C1s, the primary product of activation with C1r, C1s(I), may be susceptible to further cleavage of its H chain without any loss of C1s activity, resulting in the formation of C1s(II), though the active principle responsible for this conversion remains to be elucidated.


Classification of loops of lampbrush chromosomes according to the arrangement of transcriptional complexes. The arrangement of transcriptional units in the loops of lampbrush chromosomes from oocyte nuclei of urodele amphibia and from primary nuclei of the green alga Acetabularia have been studied in the electron microscope using spread preparations. Loops with different patterns of arrangement of matrix units (i.e. to a first approximation, transcriptional units) can be distinguished: (i) loops consisting of one active transcriptional unit; (ii) loops containing one active transcriptional unit plus additional fibril-free, i.e. apparently untranscribed, intercepts that may include 'spacer' regions; (iii) loops containing two or more transcriptional units arranged in identical or changing polarities, with or without interspersed apparent spacer regions. Morphological details of the transcriptional complexes are described. The observations are not compatible with the concept that one loop reflects one and only one transcriptional unit but, rather, lead to a classification of loop types according to the arrangement of their transcriptional units. We propose that the lampbrush chromosome loop can represent a unit for the coordinate transcription of either one gene or a set of several (different) genes.


Scanning electron-microscopical and other observations of sperm fertilization reactions in Limulus polyphemus L. (Merostomata: Xiphosura). Sperm fertilization reactions of Limulus polyphemus were examined by scanning electron and/or light microscopy. The following were considered: sperm motility, attachment of sperm to egg, acrosome reaction, and penetration of the acrosomal filament. The spermatozoa after semination are non-motile and become active only in close proximity to a defined region surrounding the egg. Egg materials diffusing into this region induce sperm motility and stimulate large numbers of spermatozoa to move towards the egg surface. Each sperm initially attaches by the apical tip and undergoes the acrosome reaction which causes a more permanent secondary attachment by the adhesion of acrosomal contents to the egg surface. The acrosome reaction also initiates the penetration of the acrosomal filament through the egg envelope, an event occurring in 70-80% of the attached spermatozoa (about 10(6). Shortly after this penetration, a secondary reaction occurs which involves a spiralling of the flagellum and an incorporation into the sperm body of the flagellar fibrous components, which then become closely apposed to the sperm nucleus. These sperm fertilization reactions were performed or initiated with 0-34 M CaCl2 in whole eggs, egg sections, excised egg envelopes and/or the outer basement lamina of the egg envelope. The Limulus fertilization system is very valuable since sperm reactions can be examined biochemically, which may lead to a better understanding of the chemical mechanisms involved in sperm-egg interactions in all animal species.


Signal emission and signal propagation during early aggregation in Dictyostelium discoideum. Waves of chemotactic movement during the early phase of aggregation in Dictyostelium discoideum are of 2 kinds, concentric waves produced by cells that emit cyclic AMP signals spontaneously, and spirals generated by excitations relayed continuously around loops of excitable cells. The period of a spiral wave is the time taken for the excitation to make one complete circuit of the pacemaker loop. We have compared signal emission from the 2 types of source in time-lapse films made at a variety of temperatures. Our results show that spiral waves have a characteristic period length throughout most if not all of the early phase of aggregation, and that the period of concentric waves is generally longer and more variable. Temperature has a pronounced effect on period length and a lesser effect on propagation velocity. We find that each individual wave is propagated at constant velocity over distances of 1-2 cm but that the velocity of successive waves declines. This decline probably reflects some cumulative effect of the chemotactic excitations on the excitable properties of the aggregating cells.


Angiosarcoma of pelvis presenting clinically as tuberculosis of hip.


Comparative study on cytological differences between high- and low-metastatic cloned cell lines of rat uterine adenocarcinoma.


Altered calcium conductance in pawns, behavioural mutants of Paramecium aurelia. Pawns are behavioural mutants (in one of three genes) of Paramecium aurelia that have lost, to varying degrees, the reversal response which is thought to depend on the calcium influx during excitation. This report shows that all of the single and double mutants have reduced active inward (calcium) current, the reduction correlating with the degree of behavioural deficit. All of the mutants display normal resting potential, input impedance and delayed rectification. Mutants in genes pwA and pwC show normal anomalous rectification, but pwB mutants do not show anomalous rectification until the membrane is hyperpolarized further. We suggest that the pwA gene plays a role in depolarization sensitivity (the 'gate') and the pwB gene a role affecting either the wall of the channel itself or the total number of channels.


Calcium channel stability measured by gradual loss of excitability in pawn mutants of Paramecium aurelia. Mutants of Paramecium aurelia that are unable to reverse swimming direction are called pawns. They lack the inward ionic (calcium) current required for the upstroke of the electrically excitable membrane response. By following the progressive loss of reversal response and excitability in cells that are suddenly changed from a heterozygous (wild-type) state to a homozygous mutant state, an estimate of the stability and mean lifetime of the calcium channel has been obtained. During rapid growth, channel dilution due to division occurred, but no channel decay was observed. Under conditions of slow growth, decay could also be observed; channel lifetime was found to be from 5 to 8 days.


The role of environmental calcium in freshwater survival of the marine teleost, Lagodon rhomboides. (1) The marine teleost fish, Lagodon rhomboides, can only tolerate fresh water (5 mM Na) if Ca is also present (10 mM). Transfer to Ca-free fresh water is followed by a substantial increase in radioactive Na efflux with little or no change in the transepithelial potential. Addition of the chelating agent EDTA (2 mM) further increases Na efflux. Fish left in Ca-free fresh water for 2-5 h die with a total body Na less than 50% of that found in animals acclimated to Ca-supplemented fresh water. (2) Rates of Na uptake were measured on either sea-water-acclimated or Ca-supplemented fresh water-acclimated fish transferred to various low Na media. In both cases Na uptake has a high Km, is saturable, inhibited by external NH4, H and amiloride, and is not related to changes in the trans-epithelial potential. (3) It is suggested that L. rhomboides is dependent upon external Ca to decrease diffusional Na loss in low salinities so that a relatively inefficient Na uptake can balance diffusional and urinary Na loss.


Growth of fertilized one-cell rabbit ova to viable morulae in the presence of pyruvate or fatty acids [proceedings].


Effects of removing foetuses from pregnant rat uteri on uterine collagen content [proceedings].


Blood flow of the lower limb in maximal treadmill and bicyle exercise.


Fluid therapy in canine babesiosis.

Fluid therapy in canine babesiosis.


Theoretical and therapeutic potential of indoleamine precursors (4).


Chromosome 8 trisomy mosaic syndrome.

Chromosome 8 trisomy mosaic syndrome.


Correlation coefficients of pattern intensity of fingers (PI) in twin families.


Position of axial triradius in 51 cases of 47, XXY Klinefelter's syndrome.


The demonstration of the silent PGM allele in a Japanese family.


Further studies on phosphoglucomutase-1 phenotypes in Japanese. i. Comparison of "slow" variants.


A genetic study of orthostatic responses and orthostatic dysregulation.


Activation of therminal components of human complement by a trypsin-activated complex of human factor B and cobra venom factor. Cleavage of C3 by CVF-B was demonstrated by hemolytic, immunoelectrophoretic and immune adherence reactions. No cleavage of C5 was detected by immunoelectrophoresis, but C5 hemolytic activity, assayed with EAC1423, decreased although less than C3 hemolytic activity. The co-existence of C3 with limiting amounts of C5 did not reduce the final degree of hemolysis of guinea pig erythrocytes (GPE) induced by late-acting components C6 through C9 and CVF-B. Thus, a CVF-B hemolytic system composed of GPE, C5 through C9 and CVF-B provided a method for titration of terminal components of human complement. CVF-B was able to generate hemolytically active sites of C567 on GPE by activation of C5, C6 and C7. The complex C567 in the fluid-phase decayed within 1 min but C567 on GPE was quite stable. Originally insensitive sheep erythrocytes became sensitive to the CVF-B hemolytic system if C3b sites were present, suggesting that cell-bound C3b played a role in orienting the positions of C567 to be fixed. CVF-B could be recovered quantitatively from the supernatant of the reaction mixture in which the hemolytically active intermediate GPEC-5678 had been formed through the interaction between C5 to C8 and CVF-B.


The pharmacological basis for modern diuretic therapy.


Renal physiology from past to present.

Renal physiology from past to present.


Improvement of findings on bone image in prostatic cancer following testosterone potentiated 32P therapy.


An attempt to create spleno-systemic anastomosis in the rat. A selective diversion of the splenic venous flow into the systemic circulation was attempted in the rat. A combination of the subcutaneous splenic transposition and the ligation of the splenic vein as a two stage operation was carried out in 15 rats. A rich collateral system developed rapidly from the transposed spleen to the systemic circulation. Angiography, performed four weeks after the ligation, revealed that almost all of the injected contrast medium was diverted into the systemic circulation via those newly developed collaterals. The described method as an experimental model could be of value in the search for a spleno-hepatic axis.


Treatment of acute alcoholism.

Treatment of acute alcoholism.


A method for measuring footpad swelling in bats.


Entrainment of the adrenal rhythm to photoperiod prior to puberty: effects of early experience on the adrenal rhythm and puberty. The purpose of this study was to determine whether exposure to a cycle of light and dark before the onset of the adrenal rhythm would be necessary in order for rats to develop a normal rhythm of peripheral corticosterone when placed in a test photoperiod at weaning age. Rats were reared in constant light (LL) until weaning age, at which time they were placed in a cycle of 14 h light, 10 h dark (14:10). Females born and reared in 14:10 had peak corticosterone values at 14.00 h on days 22 and 26, and at 18.00 h on days 32 and 36. Males did not display a clear-cut rhythm at 22 or 26 days but had peak corticosterone at 18.00 h on days 32 and 36. Males and females reared in LL until weaning had no rhythm as a group in 14:10 at 24 days of age, but had a corticosterone peak at 18.00 h on days 28 and 40. Females born and reared in LL and exposed to 14:10 for 1 day developed an adrenal rhythm regardless of the age at exposure, but only 25 day old animals showed a normal pattern for their age group. Puberty was advanced in rats exposed to a single day of 14:10 at 25 days of age, but was delayed in younger rats (22 days old), and was unaffected by light exposure in older rats (28 days of age). It can be concluded that early exposure to light-dark cycles is not required for the normal development of an adrenal rhythm in the weanling rat, and that the setting of the corticosterone rhythm to the photoperiod can occur quite rapidly. Rats at 25-26 days of age are able to respond differently to a light cycle challenge than younger rats. A photoperiodic stimulus at that time can advance the onset of puberty.


Modifications of the striatal dopamine metabolism during the estrus cycle in mice. The metabolism of striatum dopamine (DA) was studied in mice during proestrus, estrus and diestrus. The following results have been obtained: (1) the concentration of DA is higher in diestrus than in proestrus and estrus; (2) the concentration of its metabolite, homovanillic acid (HVA), is maximum in the estrus phase; (3) the DA turnover, evaluated by measuring the DA disappearance after blocking synthesis with methyltyrosine, is faster in estrus than in the other phases. These results have been discussed in view of the possible role of dopaminergic mechanisms in the control of gonadotropin secretion.


Reversible deafness as model of pressure damage to the VIIIth nerve. Frequency-specific compound action potentials (CAP) of the VIIIth nerve were registered in patients in which surgery confirmed retrocochlear pathology. A different pathologic behaviour of threshold latency was encountered for 2 and 4 kHz CAP, respectively. This was due to the question of whether transmission of neural information by the acoustic nerve's fibres was blocked completely by retrocochlear pathology or not. A totally reversible hearing loss in a case of cystic arachnitis can offer a reasonable explanation.


Experimental labyrinthine lesions through stylomastoid foramen. It was confirmed that the substances injected into the facial nerve through the stylomastoid foramen, reached every part of the inner ear. In sensitized animals, by repeated provocative injections of antigen, acute reversible episodes, very similar to that of Ménière's disease, were observed. The injection of various solutions and the provocative injection into the sensitized animals, resulted in completely opposite reactions. In sensitized animals, the electrophysiological phenomena of the cochlea also showed fluctuations like Ménière's disease.


Solitary schwannoma of the cervical vagus nerve. A case of benign, solitary schwannoma of the cervical vagus nerve with ipsilateral vocal cord paralysis is presented. The differential diagnostic aspects are discussed, with special reference to neurologic deficit in association with this lesion. The possible occurrence of concomitant unrelated malignancy is emphasised.


Rhinoscleroma: a scanning electron-microscopic study. Nasal biopsies from 6 patients with rhinoscleroma were studied by scanning electron microscopy. Numerous bacilli of different sizes were found on the epithelial surface. Few bacilli with thin spiral terminal cilia were seen over the surface of large protruding non-epithelial cells. These cells appeared to be the Mikulicz cells migrating from the tunica propria to the epithelial surface through small ulcerations. In the tunica propria, Mikulicz cells containing numerous bacilli were observed. In 4 patients, round bodies and long tubular structures were found on the epithelial surface. These bodies were suggested to be fungi, yet their exact nature and their relation to Klebsiella rhinoscleromatitis bacilli need further investigation.


Occurrence of amatoxins in Amanita ocreata.


An unusual stingray injury--the skindiver at risk. Serious abdominal injury following a stingray attack on a skindiver is described. Knowledge of the creature's habits and the avoidance of swimming along the seabed are recommended as precautionary measures against such an injury.


Dietary salt and round heart disease in turkey poults with a note on the minimum level of supplementary salt necessary in corn-soybean diets. Round heart disease in turkey poults has been associated with high levels of dietary salt and when it occurs in the field recommendations often include a reduction in the level of dietary salt. Poults fed diets containing up to 1.5% salt and 1.5% sodium did not exhibit signs of round heart disease. A high mortality rate occurred with poults fed a salt-free diet. Post-mortem analysis generally revealed enlargement of the kidneys with urates; exudate was present in both abdominal and thoracic air sacs. Growth trials indicated that in order to maintain an optimum feed:body weight gain ratio, corn-soybean diets should contain at least 0.1--0.2% supplemental salt, and at least 0.2--0.3% salt when growth rate is considered. Minimum salt levels could not be reduced further by adjustment of the total dietary sodium:chloride ratio to unity.


Social implications for the rehabilitated patient.


The microbiology of the red meat carcass and the slaughterhouse.


Woman dancing dreaming: Psychosocial benefits of the aboriginal outstation movement. The establishment of an Aboriginal outstation, or small autonomous community, is described. Some of the beneficial psychosocial changes observed during an eighteen-month period are described, and some possible reasons for them outlined. The outstation movement is presented as a viable, Aboriginal-initiated solution to some of the dilemmas facing present-day Australian Aborigines.


Molecular weight distribution of RNA fractionated on aqueous and 70% formamide surose gradients.


Translational control in embryonic muscle.


The preterm baby.

The preterm baby.


Monozygotic twins discordant for schizophrenia: a review.


Unusual masses in the spermatic cord: report of six cases and review of the literature. Differential diagnosis of spermatic cord swellings includes direct inguinal hernia, hydrocele, spermatocele, hematocele, lipoma, tuberculosis, and filariasis. This communication focuses attention on other unusual swellings of the spermatic cord. Three cases of sarcoma, two cases of foreign body in the spermatic cord, and one case of vasitis are presented. Although unusual, these conditions should be considered in the differential diagnosis of spermatic cord swellings.


Brain abscess caused by Cladosporium trichoides (Bantianum): a case with paranasal sinus involvement. Dematiacious fungi (ie, fungi with dark hyphae) are a rare and usually fatal cause of central nervous system infection. Cladosporium trichoides has been implicated most frequently. Documentation of extra-CNS involvement has been rare. Our patient had a brain abscess and paranasal sinus infection due to C trichoides. The organism was sensitive to less than or equal 2mug/ml of flucytosine. Although our patient did not receive flucytosine, it is possible that this drug, because of its excellent penetration into the cerebrospinal fluid, may be a useful therapeutic agent in cerebral cladosporiosis.


Isolated galactorrhea with normal serum prolactin levels: clinical implications. Detailed endocrine-metabolic studies were performed on five women who were otherwise well but who had had inappropriate breast secretions for variable periods of time (three months to 16 years). Our results suggest that the presence of a lactose-containing breast secretion, which strictly defines galactorrhea, does not necessarily indicate a recognizable abnormality if normal hypothalamic-pituitary function is present. In these regularly menstruating women with isolated galactorrhea, we suggest a minimum initial evaluation, but careful long-term follow-up studies to identify those cases which may progress to the other recognized, more serious amenorrhea-galactorrhea syndromes.


Social work information and accountability systems in a hospital setting. Information and accountability systems for departments of social work are a major concern for the profession, particularly within the health care sector. This paper describes the development of such a system within a large university hospital, the forces that led to its development, and the multiple expectations for its usefulness in planning and implementing social work services most effectively, within the lowest cost. It includes potential for building research projects and is utilized as a communication mechanism for recording. Collaboration within the profession is essential for implementing objective standards to be utilized in reviewing delivery of professional social work services.


The urethral pressure profile: an aid in evaluation and management of urinary incontinence in children.


Targeted mass treatment: a new approach to the control of schistosomiasis.


Nd:Yag laser.

Nd:Yag laser.


The use of CO2 laser in otolaryngology: a progress report. Since 1971 the CO2 laser has been used in otolaryngology at Boston University School of Medicine, University of Illinois, and the Eye, Ear, Nose, and Throat Hospital, New Orleans; over 560 patients have been cared for and over 1,000 operations performed. The instruments have proved to be reliable and the use of CO2 laser relatively free of complications when appropriate precautions are taken. The nature of the laser wound is such that laser surgery has facilitated the management of numerous benign and malignant lesions of the larynx as well as the oral cavity, pharynx, and tracheobronchial tree. Laser surgery is associated with a minimal morbidity, excellent healing, minimal scar formation, and excellent residual function. The instrument has been most useful in the management of lesions situated in relatively inaccessible areas such as the nasopharynx, subglottic area of the larynx, and tracheobronchial tree. The advantages of laser surgery in otolaryngology are so significant that it can be recommended for continued usage. Many applications of this unique surgical instrument have been identified but others need to be explored in the future.


The evaluation and treatment of superior oblique muscle palsy.


Evaluation of the epidemic potential of western equine encephalitis virus in the northeastern United States. The problem of evaluating the epidemic potential of western equine encephalitis in the northeastern United States is presented and possible reasons are discussed for the present lack of human and horse cases of this disease even though increased numbers of isolations of the virus have been obtained in the East during recent years. Epidemiologic factors of vector bionomics and virus strain variations are considered. It is concluded that while this virus strain can no longer be regarded as uncommon in the Northeast, the evidence indicates there is little potential for epidemic expression of this agent in the human and horse population. This appears to be due to differences in the bionomics of the mosquito Culiseta melanura, which serves as the primary enzootic vector in the northeastern United States and in the bionomics of Culex tarsalis that is the vector in the western region of the United States. Other limiting factors in the epidemic potential may be variations between virus strains located in the East and West.


The effect of lead on cells cultivated in vitro. II. Chronic exposure and development of resistance. In a previous communication the acute effects of anorganic lead salts on L-A mouse fibroblasts cells cultured in vitro have been described. This report presents the results of long-term tests with L-A cells. Under continuous exposure lead tolerance developed, even to concentrations exceeding the LD50. The kinetics of the acquirement of resistance are demonstrated. The resistant cells adjusted more quickly to higher doses of the heavy metal than the controls. Low-resistance strains retained the growth characteristics of the parent cells, but with increasing levels of lead tolerance multiplication rates decreased significantly. After approximately 60 generations in lead-free environment the cells had to a major degree lost their resistance indicating that the induced lead tolerance is caused by adaptation rather than by mutation and selection. Lead resistance appears not to depend on lead exclusion, for the lead content of resistant cells and lead-exposed controls was found to be of a comparable order of magnitude.


Breast cancer in identical twins. A case report.


On the significance of nipple discharge in the diagnosis of breast disease. Nipple discharge, especially the blood-stained type, is regarded as an important symptom in breast disease. In many reports the high incidence of malignancy is stressed and an active surgical approach has often been recommended. In this series of 80 women with nipple discharge the type of secretion and the result of exfoliative cytology were evaluated. Three women had cancer but the nipple discharge was important for the diagnosis in only one case. Six women had papilloma and in all the nipple discharge was essential for the diagnosis. Fibroadenosis and duct ectasia were the most common diagnoses. The blood-stained secretion was due to fibroadenosis in about half of the cases. No cancer was found in 46 women with a serous secretion. When a tumour is present nipple discharge is of little importance for the diagnosis and treatment. In the absence of a tumour and when exfoliative cytology gives no suspicion of cancer and no atypical cells or papillomatous clusters are present, an expectant attitude towards surgery seems satisfactory. With such an approach many surgical biopsies prove unnecessary, but a prerequisite is an organized follow-up.


Treatment of Paget's disease of bone with salmon calcitonin.


Studies on the effects of repetition of insufficient activation with butyric acid and benzimidazole in the sea urchin egg.


Interaction of methylpredonisolone with adrenergic bronchodilators in isolated guinea pig tracheal strips.


The influence of propanediol-1,3 on the development of the legs, wings and lower beak of the chick embryo. In seven series of 31-34 chick embryos each, the influence of the position of the egg during incubation and of the administration of 0.05 ml propanediol-1,3 on the 5th day of incubation on the development and growth of the limbs and beak were studied. Isotonic saline injected embryos served as controls. The embryos were sacrificed at the age of 15 days. Incubation of the egg in a vertical position, with the air chamber pointing upward, proved to result in a slight, through significant reduction in the length of the limbs and beak. Propanediol was highly toxic if injected in the immediate vicinity of the embryo. If injected at some distance from the embryo, either into the air chamber or into the yolk, the agent proved to be teratogenic: measurements showed a considerable retardation of the longitudinal growth of the limbs and beak, the latter being a parrot beak in 60 per cent of the cases, whereas both the tibia and the metatarsals were, moreover, bent posteriorward. Histological studies of the tibia showed an underdevelopment of the periosteal bone collar and, at the angle of the bone, a replacement of the posterior part of this collar by endochondral bone trabeculae. The abnormalities observed are dissimilar to those demonstrated in hereditary congenital chondrodystrophy and in micromelic conditions induced by insulin or sulfonamides.


The fine structure of the epithelium of prostate glands in adult female mastomys erythroleucus Temm. The prostate glands in adult female Mastomys were studied with the light and the electron microscope. In the light microscopy, each prostatic acinus is lined by a single layer of tall cuboidal secretory epithelial cells which are surrounded by a capsule composed of a few layers of elongated and flattened cells. The acinar secretory epithelial cells show no presence of the supranuclear light areas in their cytoplasm and tend to be more readily stained with toluidine blue in the perinuclear and the upper basal cytoplasm than in the rest cytoplasm. In the electron microscopy, sharply localized pittings are occasionally found on the luminal surface and further the secretory granules which are closely situated to the apical cell surface are recognized. In the supranuclear cytoplasm, several well-developed Golgi apparatuses appear individually and early developing secretory granules are also observed. In the perinuclear and the upper basal cytoplasm the rough endoplasmic reticulum is well developed while in the lower basal cytoplasm the smooth endoplasmic reticulum is conspicuously developed and predominates.


The absorption of nicotine from tobacco snuff through the nasal mucosa.


Passive hemagglutination miniaturized technique for pox viruses and antigen identification using formalinized erythrocytes.


Artificial induction of lactation in ewes: the involvement of progesterone and prolactin in lactogenesis. An attempt has been made to evaluate the importance of prolactin and 'progesterone withdrawal' for lactogenesis. The experimental model system used was the ovariectomized, non-pregnant ewe induced to lactate artifically by treatment with trigger hormone (either oestrogen, glucocorticoid or oxytocin) alone or in combination with progesterone. It appears from the results that prolactin is important in the lactogenic responses elicited by oestrogen and oxytocin but not as important in the response elicited by glucocorticoid. Moreover, the results suggest that, in the ewe, an appropriate positive hormonal stimulus will overcome the inhibitory influence of progesterone on lactogenesis.


The suppressive effect of halothane on DNA synthesis of immunocytes. Mice, previously immunized with sheep erythrocytes, were anaesthetized with halothane and the splenic lymphoid cells were incubated with 3H-thymidine at 1-h intervals. Abiphasic response was observed; 0.9 and 1.5% halothane reduced 3H-thymidine incorporation into the primed lymphoid cells by 83 and 94% respectively, while 0.4% halothane stimulated it by 5% of control at 3H. Immunosuppression by halothane may be the result of reduced 3H-thymidine uptake of the dividing immunocytes.


Evaluation of an intermittent schedule of dibromodulcitol in breast cancer. Dibromodulcitol was administered orally on Days 1-10 every 3-4 weeks to 29 patients with metastatic breast carcinoma refractory to previous combination chemotherapy. Initial doses between 70 and 280 mg/m2/day were utilized. The dose was escalated as tolerated in subsequent cycles in individual patients. Hematosuppression was dose-limiting. At doses of greater than 200 mg/m2/day leukopenia (greater than 1000 cells/mm3) and thrombocytopenia (greater than 25,000 platelets/mm3) occurred in one of 28 cycles and two of 27 cycles respectively. In contrast, at doses of less than or equal to 200 mg/m2/day leukopenia and thrombocytopenia occurred in four of 18 cycles and five of 18 cycles respectively. Recovery of leukocytes (less than 4000 cells/mm3) and platelets (less than 100,000 platelets/mm3) by Day 29 after the start of therapy was also delayed at higher doses. Responses were observed in three of 29 evaluable patients and subjective improvement of osseous disease in one additional patient. A dose of 180 mg/m2/day X 10 Every 28 days is recommended in previously treated patients to avoid severe hematologic side effects.


Rapid analytic method for adriamycin and metabolites in human plasma by a thin-film fluorescence scanner. A rapid and highly sensitive method is described for the quantitative determination of adriamycin and metabolites in plasma. Adriamycin (Ad) with daunorubicin added as the internal standard was extracted from plasma with chloroform-isopropanol (1:1), separated by thin-layer chromatography (TLC), and quantitated in situ via a fluorescence scanning technique. This method represents one of the very few reliable quantitative TLC methods and is suitable for the routine determination of Ad in plasma in amounts as low as 2 ng/ml. Plasma Ad levels at 24 hours in rabbits and in patients both given a 1-mg/kg dose, previously regarded as difficult to be measured, are now easily measurable using as little as 0.5 ml of plasma. Multiple samples (ten to 15) can be analyzed by this method within a day.


Interactions of antiestrogens with human breast cancer in long-term tissue culture. A variety of antiestrogens can be shown to antagonize estrogen action in animal model systems. Several of these compounds are useful in the management of metastatic human breast cancer. To further elucidate their mechanism of action, we studied several of these compounds using human breast cancer cell lines maintained in long-term tissue culture as a model system. Antiestrogens including tamoxifen (NSC-180973; ICI-46474), nafoxidine. CI-628, and clomiphene citrate inhibit macromolecular synthesis below control levels in two human breast cell lines. This effect is limited to cell lines which contain estrogen receptors. Simultaneous addition of as little as 1000-fold less estradiol prevents antiestrogen effects. Sequential addition of estrogen for up to 48 hours to cells incubated in antiestrogen reverses inhibition. If cells are continued in antiestrogen alone for more than about 3 days, inhibitory effects become irreversible. The cells detach from the surface of the culture vessel and are no longer viable. Tamoxifen competes with 3H-estradiol for specific receptor sites but with about a 100-fold lower apparent affinity. Direct binding of 3H-tamoxifen and 3H-estradiol to duplicate cytoplasmic extracts reveals equivalent numbers of binding sites but a 20-fold lower affinity for the antiestrogen. There is reasonable agreement between concentrations of tamoxifen which bind to receptor and concentrations which inhibit cells. Several antiestrogen compounds were studied using human breast cancer cell lines maintained in long-term tissue culture.  Tamoxifen, nafoxidine,  CI-628 (nitromifene citrate), and clomiphene citrate were shown to inhibit macromolecular synthesis below control levels, but only in 2 human breast cancer lines containing estrogen receptors.  This antiestrogen effect was prevented by the simultaneous addition of 1000-fold less estradiol-17.  Sequential addition of estrogen for up to 48 hours to cells incubated in antiestrogen reversed the inhibition but after 3 days of incubation with only antiestrogen, the effect was not reversible.  Tamoxifen competed with tritiated-estradiol for receptor sites but with much less affinity.  Direct binding of tritiated-tamoxifen and tritiated-estradiol revealed equal numbers of binding sites.  The antiestrogen had a 20-fold less affinity for the binding sites.  All other antiestrogens studied similarly inhibited cells to below control levels.  It is concluded that antiestrogens do not act by simply competing with estrogen for receptor sites.  Nuclear binding of the antiestrogen complexes has been shown to be different from estrogen-receptor complexes.


Phase I study of oral mitomycin C.

Phase I study of oral mitomycin C. This study demonstrates that the gastrointestinal absorption of oral mitomycin C is variable and that myelosuppression correlates most closely with the peak serum concentration. The probable maximal-tolerated dose of oral mitomycin C is 45-50 mg/m2.


Phase II study of methyl-CCNU in the treatment of advanced pancreatic carcinoma.


Interaction between serum albumin and mercaptoundecahydrododecaborate ion (an agent for boron-neutron capture therapy of brain tumor). I. Introductory remarks and preliminary experiments.


Interaction between serum albumin and mercaptoundecahydrododecaborate ion (an agent for boron-neutron capture therapy of brain tumor). II. Proposal of two interaction models.


Interaction between serum albumin and mercaptoundecahydrododecaborate ion (an agent for boron-neutron capture therapy of brain tumor). III. Results of analysis.


Effect of inorganic sulfur and selenium on O2-uptake and aniline hydroxylation by dithiothreitol-iron complex in comparison with adrenodoxin and Se-adrenodoxin.


Preparation of a specific antibody to each one of catecholamines and L-DOPA.


Subunit structure of 27 S thyroid iodoprotein. The dissociation of thyroid 27 S iodoprotein by sodium dodecyl sulfate (SDS) and by succinic anhydride was investigated by means of ultracentrifugation and polyacrylamide gel electrophoresis. The iodoprotein obtained from either a human or hog was dissociated into three kinds of subunits (S-19, S-17 and S-12) by SDS treatment. At increased concentrations of SDS, the S-12 subunit was predominant among the dissociation products. The succinylation of 27 S iodoprotein showed essentially the same dissociation pattern as in the case of SDS treatment. This dissociation products of the protein preparations of different animals were qualitatively the same as those of thyroglobulin of the respective animals, confirming the hypothesis that 27 S iodoprotein was composed of two molecules of thyroglobulin. However, the extent of dissociation of 27 S iodoprotein measured by S-12 formation showed higher resistancy of the protein to the dissociating agents than that of thyroglobulin. The contents of sialic acid and hexose as well as iodoamino acids of 27 S iodoprotein were found to be the same as, or not far from, those of thyroglobulin; The dissociability and chemical composition of 27 S iodoprotein was discussed with reference to the subunit structure of the protein.


A model for evaluation of the peroral insulin therapy: short-term treatment of alloxan diabetic rats with oral water-in-oil-in-water insulin emulsions. Alloxan diabetic rats with fasting blood glucose levels above 300 mg/100 ml were treated with oral administration of water-in-oil-in-water (W/O/W) insulin emulsions at a dose of 50 U/100 g body weight, three times daily for 10 to 14 days. The course of diabetes was followed by determinations of glucose levels in blood and urine. During treatment with oral W/O/W insulin emulsions, daily excretion of urinary glucose decreased by about 30 to 40% (2 to 3 g/day) in all of the five rats studied, and returned to the pre-treatment levels after the treatment being discontinued. During treatment, a significant reduction in fasting blood glucose levels was observed in 4 out of 5 rats, giving the decrease by 18 to 44%. Quantitative estimates suggested that the effectiveness of 50 U/100 g of oral W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at a dose of 0.5 U/100 g. Although oral W/O/W insulin emulsions are still of low efficiency, these results would indicate that diabetes can be controlled by effective oral insulin preparations.


Pituitary function in reproductively senescent female rats.


Olfactory discrimination as an isolating mechanism in speciating mole rats. Olfactory discrimination was tested in two chromosome forms of the speciating fossorial rodent, Spalax ehrenbergi, in Israel. Females of the chromosome forms 2n = 52 and 2n = 58 were tested for male odour discrimination, the source of odour being either case litter or urine. Estrous females of both forms preferred homochromosomal odurs, whereas diestrous females showed no discrimination. These results suggest that olfactory discrimination may serve as a reproductive isolating mechanism in the speciation of mole rats.


Fine structrual relation between pancreatic excretory ductules and intercellular spaces. Horse-radish peroxidase injected into the femoral vein of intact rats, or infused at 30 cm H2o pressure into the main pancreatic duct of intact dogs, entered easily the interstitial spaces surrounding acini and acinar cells. The latter are interconnected at their luminal segments by zonulae occuldentes. These junctions form a barrier to tracer penetrating from the interstituim towards the lumen of terminal ductules. However, the intraductally infused peroxidase entered the interstitial spaces, probably through the pressure injured acinar cells, as did colloidal carbon particles when infused intraductally.


Evidence of diurnal fluctuation of sensitivity to noradrenaline in the rat-the role of the thyroid. The capacity for heat production, under the influence of the same amount of noradrenaline, in the rat was significantly higher in the evening (20.00 h) than in the morning (07.00 h). Thyroidectomy produces not only a lower level of heat production, but also a complete disappearance of the differences between the morning and the evening experiments.


Assortative mating between chromosome forms of the mole rat, Spalax ehrenbergi. Females of two parapatric chromosomal forms (2n = 52 and 2n =58) of the fossorial mole rat, Spalax ehrenbergi, in Israel, were tested for mate selection between two alternative, a homo- and a heterochromosomal, males. Estrous females significantly preferred the male of their own chromosomal form, on the basis of several behavioural criteria. The evolutionary significance of the positive assortative mating found, lies presumably in reinforcing reproductive isolation between the chromosome forms, thereby contributing to finalize speciation.


Foetal blood abnormality associated with hypodactyly in the hd strain of rat. The homozygous foetuses of hypodactyl rats (hd strain) present an obvious red blood cell macrocytosis (day 14 of gestation). This blood abnormality could give rise to thrombosis leading to early necrosis of the extremities.


Ethanol production during the growth cycle of Aureobasidium pullulans.


Incorporation of [14C] palmitate into the lipids of cultured chick-embryo myoblasts.


The effect of low concentrations of prostaglandin E1 on myoblast fusion.


Steroidal control of protein synthesis in the developing chick embryo.


Polyadenylated ribonucleic acid in normal and scrapie-infected mouse brain.


Control of cell differentiation in the cellular slime mould Dictyostelium discoideum.


Serum levels of gonadotropins during lactational amenorrhoea.


Uric acid in pregnancy and toxaemia.

Uric acid in pregnancy and toxaemia.


Post partum vaginal smear in lactating and non-lactating.


[Changes in the substantia nigal self-stimulation behavior caused by intraventricular injection of norepinephrine, dopamine and GABA]. A bipolar electrode was stereotaxically implanted in the substantia nigra of male albino Wistar-Imamichi rats. Effects of l-norepinephrine (NE), dopamine (DA) and gamma-aminobutyric acid (GABA), injected into the lateral ventricle, on the substantia nigral self-stimulation (SS) behavior, and the effect of alpha- and beta-adrenergic receptor antagonists on the facilitation induced by NE were investigated. NE but not DA facilitated the SS behavior and GABA showed no constant effects on the behavior. Facilitation by NE of SS behavior was inhibited by phentolamine, but not by propranolol. These results suggest that the noradrenergic system in the brain may play a more significant role in the positive reinforcement of the substantia nigral SS behavior than does the dopaminergic or GABA-ergic system, and that the action of NE may be facilitated through alpha-receptors rather than through beta-receptors.


Genetic characterization of methotrexate-resistant chinese hamster ovary cells. In a previous report, we described the selection and partial characterization of three methotrexate (Mtx)-resistant Chinese hamster ovary cells (CHO) (1). Class I cells contained an apparent structural alteration in dihydrofolate reductase. Class II cells had an alteration affecting the permeability of the drug. Class III cells, selected from Class I cells, had an increased activity of the altered enzyme. In the work described here, it has been shown that the spontaneous mutation rate to Class I resistance is in the order of 2 X 10-9 mutations per locus per generation and that in single-step mutagenized selections the number of resistant colonies of Class I and II are about equal. Class I and Class III resistance is expressed codominantly in somatic cell hybrids, whereas the Class II resistant marker is a recessive trait.


Time sequence and morphological evaluations of cells fused by polyethylene glycol 6000(1). Mouse L cells (clone 1D) were fused with polyethylene glycol (PEG). The fusion sequence was determined by using sequential light microscopy of the same group of cells, scanning electron microscopy (SEM),transmission electron microscopy, and freeze-etching. The cells were found to fuse only 1 min after PEG had been washed off at small localized areas. Larger fusion images were found after 3 min. Intramembrane particles were observed to have a tendency to aggregate after PEG treatment, but a direct correlation of this activity with the fusion process could not be made. No pathological changes were noted at longer times after PEG removal, except for the extensive widening of the rough-surfaced endoplasmic reticulum (RER) in some cells. It is proposed that fusion does not occur if apposing cells have many microvilli at the area of apparent contact.


Absent left pulmonary artery with left arch and subaortic stenosis.


Cytoplasmic inheritance in mammalian tissue culture cells. A series of intraspecific, interspecific and interorder somatic cell cybrids and hybrids have been prepared by fusions in which one of the parents contained the cytoplasmically inherited marker for chloramphenicol (CAP) resistance. A clear relationship has been established between the expression of the CAP-resistant (CAP-R) determinants in the fusion products and the genetic homology of the parents. With increased genetic divergence, the acceptability of the CAP-R mitochondria decreased. Intraspecific cybrids and hybrids of the same strain were stable for the CAP-R marker, while those between strains were stable only in CAP. Intergeneric mouse-hamster cybrids occurred at a high frequency but were unstable in CAP, while CAP suppressed hybrid formation 100-fold. Interorder cybrids (CAP-R human X CAP-S mouse) occurred either at a moderate frequency and were stable at a low frequency and were unstable in CAP. Interorder hybrids could only be formed by challenging HAT-selected hybrids with CAP or by direct selection in ouabain and CAP. Reciprocal interorder crosses between CAP-R mouse and CAP-S human cells were unsuccessful. Interspecific cybrids contain only the chromosomes of the CAP-S parent. Interspecific hybrids selected directly in CAP segregated the chromosomes of the CAP-S parent, while hybrids selected in HAT and then CAP segregated those of the CAP-R parent. The mitochondrial DNA(mtDNA) of all mouse-human cybrids and most HAT and then CAP-selected hybrids contain only the mtDNA of the CAP-S mouse parent. However, preliminary evidence suggests that one of these hybrids contains both mouse and human mtDNA sequences.


PSROs and the legal protection of confidential information.


Congenital dislocation of the hip in the newborn. A correlation of clinical, roentgenogrhic and anatomical findings. This study correlates roentgenography, arthrography, morbid anatomy and histology in four newborn infants with congenital dislocation of the hip. Three died shortly after birth. In two of these, manipulative reduction was impossible. Both demonstrated secondary adaptive changes at autopsy, indicating that the dislocation had been present for some time in utero. The first had a paralytic dislocation (meningomyelocele), and the second showed no pathologic findings other than the dislocated hip. The third infant had a dislocation that was reduced at birth. The child died of pneumonia on the 15th day. At autopsy, no secondary adaptive changes were found in the hip. The fourth infant, who had undergone open reduction because of a dislocation irreducible at birth, was retrospectively found to have an intrauterine dislocation when the maternal roentgenogram was reviewed. Significant secondary adaptive changes were noted at the time of operation.


Malpractice liability and PSRO. Part II.


How to overcome barriers to effective audit.


Intra-oral temperatures in man with special reference to involvement of the central incisors and premaxillary alveolar process in lepromatous leprosy. The predilection of lepromatous leprosy for body sites substantially below core temperature is well known, and within the oral cavity the premaxillary alveolar process and upper central incisor teeth are especially affected. In this study, intra-oral temperatures were recorded by means of a series of thermistor probes applied to the teeth and labial surfaces of the gums of normal subjects. The temperature distribution established showed a close correlation with the known pattern of involvement of teeth and supporting structures derived from clinical, pathological and archeological data. Relatively low temperature of the premaxillary alveolar process was demonstrated, a factor which may be of prime importance for the localization of disease in this region, as it is for other tissues in the lepromatous patient.


Quality health care: another administrative nightmare.


Androgenic status of lepromatous leprosy patients with gynecomastia. The androgenic status of 24 lepromatous leprosy male patients, 12 with and 12 without gynecomastia, was studied in comparison with that of 12 normal healthy males. Plasma testosterone levels were significantly diminished in the gynecomastia group as compared to levels in either of the control groups. The patients without gynecomastia showed values not significantly lower than those of normal males. Histopathologic examination of the leprous testes showed a variable admixture of inflammatory, degenerative anf fibrotic changes which were more severe and more frequent in the patients with gynecomastia than in those without it. Parenchymatous liver function tests showed greater derangement in the gynecomastia group as compared to the controls Histopathology of the liver showed lepromatous infiltration in patients with and without gynecomastia though the changes in liver were minimal in patients who showed total testicular degeneration in the biopsies.


Study of subcutaneous fat in leprosy patients.


Leprous myositis.

Leprous myositis.


Leprosy and the lipidoses.

Leprosy and the lipidoses.


A mare mule--dam or foster mother?

A mare mule--dam or foster mother? A female, horse-like foal was apparently born to a mare mule from mating to a Shetland stallion. The presence of three pregnant Shetland mares in the same pasture, however, raised some questions about parentage, even though all three mares apparently gave birth to single foals within 6 weeks after the birth of the propositus. The transferrin system indicated that the foal was not born to the mare mule but was the offspring of one of the Shetland mares. Apparently one Shetland mare gave birth to twins 3 to 6 weeks apart, and the mare mule came into lactation spontaneously and adopted the first twin. The offspring was determined to be a horse by appearance, karyotype, blood type, and voice.


Use of factor analysis to classify strains of yeasts: application to genus Torulopsis Berlese.


Effect of maternal parity on aneuploidy in early mouse embryos. An attempt to evaluate the incidence of chromosomal aneuploidy in mouse blastocysts recovered from females of various ages and parity levels revealed an insignificant regression coefficient for aneuploidy on age of the female and its square, and an insignificant correlation coefficient for aneuploidy with the number of previous offspring born to the dam. However, significant regression coefficients were obtained for aneuploidy on parity of the dam and its square. These results indicate that not only does aneuploidy increase with parity level, but the rate of increase accelerates as parity level increases. Possible explanations for the increase in aneuploidy and its detrimental effect on reproductive efficiency were discussed.


Stochastic selection in both haplophase and diplophase. A population genetic model incorporating the evolutionary forces of zygotic selection, gametic selection and non-Mendelian segregation has been analyzed for the case in which all selection coefficients and the segregation parameter are assumed to be random variables that are uncorrelated from generation to generation. The diffusion approximation of the model is developed, and the subsequent analysis shows that one of four limiting outcomes of the stochastic process may obtain--an allele may be fixed or lost almost surely and irrespective of the initial gene frequency, the gene frequency may converge to a unique stationary distribution, or an allele may be fixed or lost with probabilities depending on the initial gene frequency. These outcomes correspond rather closely with the possible outcomes of the deterministic model--fixation or loss of an allele, convergence to a stable equilibrium, or the existence of an unstable equilibrium.


Predator prey interactions with time delays. A general (Volterra-Lotka type) integrodifferential system which describes a predator-prey interaction subject to delay effects is considered. A rather complete picture is drawn of certain qualitative aspects of the solutions as they are functions of the parameters in the system. Namely, it is argued that such systems have, roughly speaking, the following features. If the carrying capacity of the prey is smaller than a critical value then the predator goes extinct while the prey tends to this carrying capacity; and if the carrying capacity is greater than, but close to this critical value then there is a (globally) asymptotically stable positive equilibrium. However, unlike the classical, non-delay Volterra-Lotka model, if the carrying capacity of the prey is too large then this equilibrium becomes unstable. In this event there are critical values of the birth and death rates of the prey and predator respectively (which hitherto have been fixed) at which "stable" periodic solutions bifurcate from the equilibrium and hence at which the system is stabilized. These features are illustrated by means of a numerically solved example.


Global stability in two species interactions.


Nucleotide precursor in riboflavin biosynthesis.


Animal experiments on thiamine avitaminosis and cerebral function. Before industrial production of thiamine becam possible, among many beriberi patients some showed symptoms of encephalopathy, the cerebral form of the disease. In this animal experiment, thiamine-deficient rats showed failure or blocking of the operant behavior in the maze box, pole climbing box and shuttle box, indicating orientation disturbance and defective memory. This Wernicke's syndrome-like sign dramatically disappeared by treatment with thiamine. Potentiated narcosis with thiopental or alcohol induced in thiamine-deficient rats and mice was readily reversible by thiamine administration. These phenomena are associated with thiamine content of the brain and are found long before histopathological changes in the brain of deficient animals. It is easily surmised that thiamine deficiency in the brain may block the brain metabolism and subsequently cause changes in any chemical substances in the brain, refracting on biophysical phenomenon, such as EEG. However, in the present study, generally speaking, no meaningful results concerning these points were obtained.


UV effect on germ cell determinant and a proposed scheme for germ cell formation process in embryos of Xenopus laevis.


Effect of deuterium oxide (D2O) on excitation-contraction coupling of skeletal muscle.


Analysis of combined effects of benzene with radiation on chromosomes in cultured human leukocytes. Three experiments were carried out on 53-hr cultured human leukocytes on chromosome mutagenicity of benzene with particular reference to combined effects with gamma-radiation and inhibitory effect on rejoining of radiation-induced chromosome breaks. The results and their analyses were summarized as follows: 1) Benzene can induce mainly chromatid-type deletions, especially gaps, suggesting that the cells in their late S-G2 stage have a higher susceptibility to chromosome breakage by benzene. 2) The aberration tield of dicentrics and rings induced by 100 rads irradiation can significantly be enhanced by the treatment of benzene equal to or in excess of 0.2 mM. 3) Quantitative analyses using newly defined "Synergetic effect factor" revealed that combined cytogenetic effect of benzene with radiation could be synergetic exclusively in dicentrics and rings, being almost additive in the other types of aberration. 4) The experiment with dosage fractionation method showed that the more strongly benzene could inhibit the rejoining of radiation-induced chromosome breaks, the higher concentration it was treated at. Related iwth these results, possible inducps, and the repair and its inhibition of radiation-induced DNA-strand(s) breaks. Further studies for related effects by benzene are needed on protein synthesis, activities of repair enzymes and fine structure of chromosomes.


Toxicity of propoxur to rats by subacute inhalation. Male and female rats were exposed to propoxur (2-isopropoxyphenyl-N-methyl-carbamate) aerosol, concentrations averaging 5.7, 18.7 and 31.7 mg/m3 air, for 6 hours daily on five days in a week over a period of 12 weeks. The effects were depressions of plasma by 20 to 30%, and of erythrocyte and brain cholinesterase activities which were caused by the highest air concentration of 31.7 mg/m3. On the basis of the physical, biochemical, phamacokinetic and metabolic behaviors of propoxur, a maximum allowable concentration of 2.5 mg/m3 air is suggested.


Cold water immersion test in patients with vibration disease. Peripheral vascular disorder is one of the most important symptoms in diagnosing vibration disease. Several kinds of tests have been introduced to evaluate the peripheral vascular function. Among those tests, cold water immersion test has been mostly applied. In Japan, the generally used method is to measure the skin temperature of one finger of the hand immersed up to the wrist joint in water at 5 degreesC for 10 minutes. However, because the suffering during the test is so severe and some unfavorable warning symptoms have been observed during group examinations, a safer and milder method is more desirable. In order to examine the applicability of the test by using water at 10 degreesC in comparison with that at 5 degreesC, and to know the degree of suffering during the tests, a comparative study was performed. Sixteen students and 29 patients with vibration disease joined in this study. The results suggest that water at 10 degreesC can be effective stimulus, if the immediate rewarming response is used for evaluation. The self-rating scores revealed that the suffering was milder in case of water of 10 degreesC than at 5 degreesC for both the students and the patients. And the patients seemed to suffer more from chest discomfort than the students.


Inhibition of repair of radiation-induced chromosome breaks. Effect of phenol in cultured human leukocytes.


Polychlorinated naphthalenes in the surrounding environment of a reproduction factory of used transformer oil.


Delayed hypersensitivity tests with Mycobacterium leprae purified protein derivative. Skin tests were conducted on 3 lepromatous, 3 dimorphous and 6 tuberculoid leprosy patients and 3 others not suffering from leprosy with lepromin, purified protein derivative from M. leprae of armadillo origin and tuberculin. Results show that a delayed hypersensitivity reaction could be produced with PPD in 72 hours on all Mitsuda positive cases, with one anomalous exception, without cross reaction to tuberculin. The results were promising from the point of view of substituting lepromin with PPD in usual tests.


Microtubules and actin filaments in teleost visual cone elongation and contraction. Teleost retinal cones contract in light and elongate in darkness. This paper describes the disposition of microtubules and cytoplasmic filaments in cone cells of 2 species of fish (Haemulon sciurus and Lutjanus griseus). In Haemulon, the neck-like "myoid" region of the cone changes in length from 5 mu to 75 mu. Maximal observed rates of elongation and contraction are comparable to that of chromosome movement in mitosis (2-3 mu/min). Microtubules presumably participate in cone elongation, since numerous longitudinal microtubules are present in the myoid region, and colchicine blocks dark-induced elongation. Myoid shortening, on the other hand, appears to be an active contractile process. Disruption of microtubules in dark-adapted cones does not produce myoid shortening in the absence of light, and light-induced myoid shortening is blocked by cytochalasin-B. Cone cells possess longitudinally-oriented thin filaments which bind myosin subfragment-1 to form arrowhead complexes typical of muscle actin. Myoid thin filaments are clearly observed in negatively stained preparations of isolated cones which have been disrupted with detergent after attachment to grids. These myoid filaments are not, however, generally preserved by conventional fixation, though bundles of thin filaments are preserved in other regions of the cell. Thus, actin filaments are poorly retained by fixation in precisely the region of the cone cell where contraction occurs. Cone cells also possess longitudinally-oriented thick filaments 130-160 A in diameter. That these thick filaments may be myosin is suggested by the presence of side-arms with approximately 150 A periodicity. The linear organization of the contractile apparatus of the retinal cone cell makes this cell a promising model for morphological characterization of the disposition of actin and myosin filaments during contraction in a nonmuscle cell.


A report on the national professional standards review council meeting May 3-4, 1976; Washington, DC.


The surface events of fertilization: the movements of the spermatozoon through the sea urchin egg surface and the roles of the surface layers. The sea urchin egg surface at fertilization has been examined with the scanning electron microscope to reveal the movements of the spermatozoon from the exterior, through the surface layers, and into the egg cytoplasm. The layers that the spermatozoon encounter have been studied to determine their physical and chemical natures and their role in early development. By studying the outside of whole eggs and the inner face of surfaces isolated shortly after fertilization, it has been possible to compile data on the movements of the spermatozoon through the egg surface. The spermatozoon initially contacts the egg with the elongated acrosomal process. The vitelline sheet, the outermost layer of the egg, separates slightly next to the attached spermatozoon. As membrane fusion between the gametes occurs, the plasma membrane from the egg engulfs the spermhead, the cortical granules start to discharge their contents, and a spreading surface deformation, concommitant with a distortion of the fibrous cortex, is initiated. A cluster of elongate microville surround the perpendicularly fusing spermatozoon. These microvilli interidigitate as the spermatozoon is forced to lie upon the egg surface between the plasma membrane and the matrix of cortical fibers. The spermatozoon then rotates additionally to enter the egg cytoplasm with the posterior end first; it has rotated 180 degrees through the cell surface. Finally, it detaches into the egg cytoplasm, leaving a scar in the cortex through which it penetrated. The egg cortex, previously unobserved by electron microscopy, is revealed to be composed of 50-200 nm fibers. At fertilization they are uniformly organized but during later development this order is lost. The cortex is from 0.2-0.5 micronm thick and is a contractile structure. The role of the outer surface in releasing the cell from the metabolic constraints of the unfertilized egg is shown, and the apparent differences in the mobilities of the membranes derived from the sperm and from the egg are demonstrated. The relation of these layers to the movements of the spermatozoon, to the activation of the egg, to the block to polyspermy, and to each other are discussed.


Confidentiality of alcohol and drug abuse patient records.


National Health Planning and Resources Development Act of 1974.


PSRO communications. Regulations--program manual transmittals--memos of understanding.


Immobilization and steroid-transforming microorganisms in polyacrylamide.


Monitoring of air and water for enzyme inhibitors.


On the potential of soluble and immobilized enzymes in synthetic organic chemistry.


Regional brain variations of tryptophan, monoamines, monoamine oxidase activity, plasma free and total tryptophan during the estrous cycle of the rat. Normal 4-day cyclic rats were sacrificed at 10 a.m. and 3 p.m. on proestrus or estrus and at 10 a.m. on metestrus. Noradrenaline (NA), dopamine (DA) and tryptophan (T) concentrations varied only slightly. Serotonin (5-HT) concentrations showed characteristic changing patterns in many hypothalamic, limbic and midbrain structures with a decrease during proestrus and an increase during estrus being observed. Monoamine oxidase (MAO) activity changes were often parallel to the 5-HT changes, but were not as great. The marked changes in 5-HT early in proestrus are a further indication of its inhibitory effect on gonadotropin release mechanisms before the 'critical period'.


Persistent estrus in rats after anterolateral hypothalamic microinjections of 6-hydroxydopamine. Bilateral injections of 30 mug of 6-hydroxydopamine (6-OHDA, as base) into the anterolateral hypothalamic area induced constant vaginal cornification (CVC), polyfollicular ovaries and uterine hypertrophy in cyclic adult female rats. There were no important changes in the vaginal patterns or ovarian and uterine morphology in animals given injections in the same area with the solvent only and in animals given injections with 6-OHDA in the anterior amygdaloid area. It is suggested that the persistent estrus after anterolateral hypothalamic injections of 6-OHDA results from lesions of central catecholaminergic pathways, which are probably involved in gonadotropin secretion.


Effects of imipramine, chlorimipramine, and fluoxetine on cataplexy in dogs. Four narcoleptic dogs with cataplexy were given trials with the serotonin uptake blockers imipramine and chlorimipramine (known to be effective in treating cataplexy in humans). An even more selective serotonin uptake blocker, fluoxetine, was also tested. Injections of placebo, test compound, and placebo were given respectively on 3 successive days. Anticataplectic effects were measured approximately 30 min, 3 hr, and 6 hr postinjection by recording elapsed time and number of cataplectic episodes during the dogs' attempts to eat ten pieces of a desired food presented in a standard fashion. Imipramine (1 mg/kg) and fluoxetine (1.5 and 3.0 mg/kg)significantly improved performance, while chlorimipramine (0.5-5 mg/kg) had no clear effect. Data were not totally consistent with the notion that serotonin uptake blockers improve cataplexy in dogs, since chlorimipramine was not effective in these animals.


A comparison of withdrawal in rats implanted with different types of morphine pellets. Time course and duration and physical dependence was investigated in rats implanted subcutaneously with 3 different types of morphine (M) pellets. Each was formulated according to the method of Gibson and Tingstand [8], but differed in surface area and hardness. Animals were maintained for 19 days after implantation and physical dependence was assessed every other day. Severity of naloxone (Nx)-induced withdrawal was quantified by the use of a composite symptom score and weight loss. Withdrawal severity was greatest following implantation of a pellet (Type C) of large surface area and low hardness rating, and least following implantation of a pellet (Type A) of small surface area and high hardness rating. Abstinence severity which resulted from implantation of a pellet (Type B) of moderate surface area and low hardness rating was intermediate. When 2 pellets were implanted the difference between Type C and B was amplified. It was concluded that formulation per se was not sufficient for specifying M pellet characteristics.


Diminished reaction to a novel stimulus during amphetamine withdrawal in rats. This experiment determined whether reaction to a novel stimulus was diminished in a dose-dependent fashion following 8 consecutive days of d-amphetamine administration. Thirty-two male rats were injected with saline, 0.5, 2.5, or 5.0 mg/kg of d-amphetamine (each N = 8). On the ninth day, all animals received saline injections and were tested (a) in the presence of a novel stimulus, or (b) in the absence of a novel stimulus. Reaction to the novel stimulus varied inversely with the dose of d-amphetamine which had been received during the drug administration period. This reduction in reaction to the novel stimulus did not seem to depend on (a) the level of amphetamine-induced sterotypy at the end of the drug administration period (b) general reduction of activity, or (c) interference by drug-conditioned responses.


Blockade of apomorphine's discriminative stimulus properties: relation to neuroleptic activity in neuropharmacological and biochemical assays. Using a food-reinforced two-lever operant conditioning procedure, rats were trained to discriminate 0.16 mg/kg apomorphine from saline. Eight neuroleptics of the phenothiazine, butyrophenone or diphenylbutylamine type were investigated for thsir ability to antagonize the discriminative stimulus properties of apomorphine. The same drugs were also assayed for in vivo antagonism of apomorphine-induced stereotyped behavior as well as for in vitro inhibition of stereospecific 3-H-haloperidol binding in rat striatal tissue preparations. The data are consistent with the hypothesis that apomorphine exerts its discriminative stimulus properties by a mechanism similar to that underlying its stereotypogenic action. The loci involved in these two phenomena are likely to be distinct.


Chelatometric determination of epicillin.


Ea rosette test for identification of FC receptor lymphocytes. I. Some technical variables.


Some aspects of the kinetics of emiocytosis in prolactin cells. Some aspects of the kinetics of emiocytosis of secretory granules were investigated in pituitary prolactin cells of lactating female rats. Most of the emiocytotic events were directed towards those areas of the cells which were covered with a basal lamina. Diameters of the secretory granules within the emiocytotic pockets and of the openings of the pockets to the exterior were measured. An inverse relationship between the size of the granule and the diameter of the foramen was noted. A mechanism is proposed relative to the processes involved in the release of secretory granules from prolactin cells.