RIT 2214, a new biosynthetic penicillin produced by a mutant of Cephalosporium acremonium. A number of lysine-requiring auxotrophs of Cephalosporium acremonium were investigated for incorporation of side-chain precursors and for accumulation of beta-lactam compounds. One of the auxotrophs, Acremonium chrysogenum ATCC 20389, producing cephalosporin C and penicillin N only if grown in media supplemented with DL-alpha-amino-adipic acid (DL-alpha-AAA), was found to use L-S-carboxymethylcysteine (L-CMC) as a side-chain precursor for the synthesis of a new penicillin (RIT 2214). No corresponding cephalosporin was detected. The penicillin present in the culture filtrate, was concentrated by adsorption on activated carbon and successive column chromatography on Amberlite IRA-68 and Amberlite XAD-4. Final purification was achieved by cellulose column chromatography. RIT 2214 was identified as 6-(D)-[(2-amino-2-carboxy)-ethylthio]-acetamido]-penicillanic acid by spectral analysis, bioactivity spectrum, elucidation of side-chain structure and finally by semisynthesis. Its biological properties were also evaluated.


A cytoplasmic inhibitor of DNA polymerase from the plasmodia of Physarum polycephalum. A factor which inhibited DNA polymerase [EC 2.7.7.7] activity was isolated from the cytoplasm of plasmodia of true slime mold, Physarum polycephalum. This factor was purified by DEAE-Sephadex and CM-cellulose column chromatographies, heat treatment and gel filtration. This inhibitor was heat-stable, insensitive to trypsin [EC 3.4.21.4] and was not digested by RNase [EC 3.1.4.22] or DNase [EC 3.1.4.5]. The molecular weight was 16,000 as determined by gel filtration, and the isoelectric point was determined to be pH 10.1. In the presence of the inhibitor, Km for DNA in the DNA polymerizing reaction was markedly increased. The inhibitory effect was eliminated by addition of excess DNA, but the addition of excess enzyme or deoxyribonucleoside triphosphates had no effect on the inhibition.


The H+/site ratio of mitochondrial electron transport. The number of H+ ejected during passage of 2e- through each energy-conserving site of the mitochondrial respiratory chain (the H+/site ratio) was measured in three ways. In each case transmembrane movements of endogenous phosphate were minimized. (1) Measurement of the uptake of weak acids during loading of mitochondria with Ca2+ demonstrated that 2.0 weak acid anions were accumulated per Ca2+ ion. Since 1.7 to 2.0 Ca2+ ions were were taken up per site, these data correspond to an H+/site ratio of 3.5 to 4.0. (2) More direct measurement of H+ ejection using the oxygen pulse technique demonstrated that the H+/site ratio was 3.0. In these experiments phosphate movements were prevented by addition of N-ethylmaleimide to inhibit phosphate-hydroxide antiport, by washing the mitochondria to remove endogenous phosphate, or by working at 5 degrees C to reduce the rate of phosphate transport. When phosphate movements were allowed, H+/site ratios of 2.0 were observed. (3) Measurement of the initial steady rates of oxygen consumption and H+ ejection following addition of substrate to aerobic, substrate-limited mitochondria yielded H+/site ratios of 2.0, which were elevated to 4.0 when phosphate transport was prevented as described above. Previous determinations of the H+/site ratio were thus underestimates due to the unrecognized movements of endogenous phosphate; our results show that the H+/site ratio is at least 3.0 andmay be as high as 4.0.


Magnesium deprivation reproduces the coordinate effects of serum removal or cortisol addition on transport and metabolism in chick embryo fibroblasts. A variety of unrelated effectors stimulate or inhibit coordinately the same array of metabolic reactions in chick embryo fibroblasts, including the uptake of 2-deoxy-D-glucose and uridine, and the incorporation of uridine and thymidine into acid insoluble material. The coordinate inhibition of these reactions by omission of serum or addition of cortisol is reproduced quantitatively by lowering the concentration of magnesium (Mg2+) in medium containing 0.2 mM Ca2+. The response times for the utilization of uridine and thymidine following the removal of addition of Mg2+ are similar to those which follow removal or addition of serum. The effect of serum on the incorporation of choline, which is not part of the coordinate response to unrelated effectors, is not reproduced by varying Mg2+ concentrations. The results support the hypothesis that the availability of Mg2+ within the cell plays a central role in the coordinate control of transport, metabolism and growth by external physiological effectors.


Stimulation of sugar uptake in cultured fibroblasts by epidermal growth factor (EGF) and EGF-binding arginine esterase. Mouse epidermal growth factor causes a rapid increase in 2-deoxyglucose uptake in stationary phase mouse (3T3) cells or human fibroblasts. Maximum effect is approximately two fold over control levels for 3T3 cells and about 50% over controls for human fibroblasts. Maximum effect on 3T3 cells is seen about two hours after addition of 10 ng/ml EGF to the culture medium. Stimulation is easily measureable within the first fifteen minutes after addition of the hormone and may be detected at hormone concentrations as low as 0.1 ng/ml. The EGF-binding arginine esterase found associated with EGF in the mouse submaxillary gland causes an enhancement of the EGF effect. In serum-free medium, the EGF effect is still readily observed, but no enhancement by the esterase is seen. SV40 virus-transformed 3T3 cells show no effect on deoxyglucose uptake after addition of 10 ng/ml EGF to the culture medium, but a response may be demonstrated after these cells are incubated for 12 hours or more in serumless medium. EFG stimulates transport of 3-O-methylglucose in stationary phase 3T3 and human fibroblasts but no EGF stimulation of alpha-amino-isobutyrate uptake in 3T3 cells is seen under conditions is reproted to inhibit intracellular degradation of human EGF by human fibroblasts, does not diminish the EGF effect on deoxyglucose uptake in human fibroblasts.


Current status of the thiol redox model for the regulation of hexose transport by insulin. Data obtained over the last two years pertinent to the thiol redox model for the modulation of hexose transport activity by insulin is summarized. The model proposes that activation of hexose transport in fat cells involves sulfhydryl oxidation to the disulfide form in a key protein component of the fat cell surface membrane. Theoretically, the rapid activation of transport by insulin may involve either the conversion of inactive membrane carriers to the active form as originally proposed, or the conversion of a low Vmax transport system to a high Vmax form. The present experiments showed that the percent inhibition of insulin-activated transport rates by submaximal levels of cytochalasin B was decreased compared to its effects on basal transport. Treatment of fat cells with N-ethylmaleimide inhibited cytochalasin B action but not transport activity. When insulin or the oxidant vitamin K5 was added to cells 5 minutes before the N-ethylmaleimide, the elevated transport activity was also resistant to the sulfhydryl reagent, but cytochalasin B retained its potent inhibitory effect on transport. The data demonstrate that unique properties characterize basal versus insulin-activated transport activity with respect to the sensitivity of cytochalasin B action to sulfhydryl blockade in isolated fat cells. The data are consistent with the concept that activation of transport activity reflects the conversion of a reduced (sulfhydryl) system characterized by a low Vmax to an oxidized (disulfide), high Vmax transport system.


Regulation of glucose transport in chick fibroblasts: bicarbonate, lactate and ascorbic acid. The rate at which chick embryo fibroblasts in primary or secondary culture transport glucose or 3-O-methyl glucose is strongly influenced by the presence of bicarbonate ion in the culture medium. Cells growing or maintained on glucose at physiologic concentration (5.5 mM) have an 8 to 10 fold higher rate of glucose uptake than their counterparts cultivated without bicarbonate. These cells also produce more lactate as a consequence of their more rapid intake of glucose. The hydrogen acceptors, methylene blue and dehydroascorbate added to the culture medium reduce the cell capacity to transport glucose and 3-O-methyl glucose to levels obtaining in the bicarbonate-free medium. There is a concomitant reduction in glucose utilized by cells during 24 hours and further reduction in lactate formed per molecule of glucose metabolized.


Retrograde urethrogram: a new technic.

Retrograde urethrogram: a new technic.


Comment on comparing the membrane transport properties of "normal" and "transformed" BALB/3T3 cells.


Studies in terpenoid biosynthesis. Part 18. Biosynthesis of culmorin.


Cooperative binding of concanavalin A to thymocyte membrane vesicles augments uptake of alpha aminoisobutyrate. (1) Membrane vesicles from rabbit thymocytes accumulate alpha-aminoisobutyrate in the presence of 0.1 M NaCl. Uptake is 1/2 maximal after about 2 min and reaches a plateau value (61 pmoles/mg protein) after 30 min. (2) Up to 25 mug concanavalin A/ml, binding of the lectin describes a sigmoid curve indicative of a cooperative process. (3) At lectin concentrations up to 8 mug/ml, lectin binding enhances the uptake of alpha-aminoisobutyrate (maximally 30%).


The mechanism of interaction between high-affinity probes and the uridine transport system of mammalian cells. The carrier of uridine transport in hamster cells in culture is highly susceptible to the inhibitory effect of probes like S-benzylated derivatives of mercaptopurine nucleosides. The interaction between the probes and the carrier is competitive and reversible and it takes place at a site different from the substrate binding site. The Ki for the most potent derivative p-nitrobenzyl-6-mercaptoinosine is 0.15 n Molar at 20 degrees C. The effect of the probes is interpreted in terms of conformational change induced on the carrier upon binding of the probe. The carrier assumes distinct conformations depending on whether it is probe-free (form A) or probe bound (form B). Kinetic as well as chemical evidence supports the predictions of the allosteric carrier model. A single component of kinetics is observed either in the absence of inhibitor (Km form A) or at high concentrations of inhibitor (Km form B). A two component kinetics is observed at intermediate concentrations of inhibitor (some carriers in form B and others in form A). The two forms have distinct Km values for uridine: form A50 muMolar and form B 250 muMolar. Two forms have also different susceptibilities to the action of organomercurials: form A is insensitive whereas form B is highly inhibited by the chemical modified of SH groups. The existence of putative allosteric sites in carriers is discussed in terms of modifier sites capable of modulating transport activities as a result of specific membrane-ligand interactions.


The carbon-13 nuclear magnetic resonance spectra of flavonoids and related compounds.


Uptake of amino acids in reconstituted vesicles derived from plasma membranes of Ehrlich ascites cells. To obtain a clearer concept of the mechanism of organic solute transport in mammalian cells, we have attempted to reconstitute a functional transport system for amino acids from plasma membranes of Ehrlich ascites cells. Purified plasma membranes were dissolved in 2% Na cholate--4 M urea, a mixture which brought over 85% of the membrane proteins into solution. After centrifugation of the solubilized material for 2 hrs at 100,000 x g, the supernatant was dialyzed in the cold for 20 hrs with additional lipid. The reformed vesicles were tested for the ability to transport amino acids. The preliminary results obtained show that the uptake of alpha-aminoisobutyric acid can be inhibited by L-methionine and much less by L-leucine as would be predicted from the known properties of alpha-aminoisobutyric transport in the intact cells. In addition, it has been possible to show accelerated efflux of intravesicular phenylalanine when phenylalanine is added to the trans side (medium side). The data are consistent with the conclusion that there is carrier mediated transport in the reconstituted vesicles.


Synthetic and biosynthetic studies of porphyrins. Part 1. Synthesis of the "S-411" porphyrin obtained from meconium.


Synthetic and biosynthetic studies of porphyrins. Part 2. Synthesis of isopempto- and isochlorocruoro-porphyrins.


Neighbouring group participation in the cleavage of some steroidal acetoxy-epoxides.


Prostaglandins. Part 4. Synthesis of (+/-)-11-deoxyprostaglandins from 2-(omega-hydroxyheptyl)cyclopent-2-enones.


Thermal rearrangement of 2,2,4,4-tetramethylthietan-3-one 1-oxide; a reaction related to the ring expansion of the penicillin S-oxides.


4,6,7-Trimethoxy-5-methylchromen-2-one, a new coumarin from Leonotis nepetaefolia.


Ultrasonic propagation properties of mammalian testes.


Gastro-intestinal nematodes of élite show dogs in Great Britain.


Stability of resistance to neguvon in the fly Musca domestica L. after cessation of laboratory selection. Stability of resistance to neguvon was studied in three strains of Musca domestica L. after selection using different numbers of generations and different degrees of resistance. It has been found that the stability of resistance to neguvon is not always the same after cessation of selection. The loss of resistance depends on the duration of selection, i.e., on the degree of homogenization of populations with respect to resistant specimens. The degree of resistance is the function of the duration of selection to the same extent as the loss of resistance depends on it. The period of time during which the insecticide has been used is of decisive importance for the stability of resistance. The process of loss of resistance, similarly to that of its development, takes its course according to a zigzag curve, but in the opposite direction. This variation of resistance, occurring also in its development, can be explained by the heterogenity of the strains.


On a new nematode Leipernema leiperi n.g., n.sp. (Strongyloididae), parasitic in the pangolin Manis pentadactyla from Hyderabad, India. Leipernema leiperi n.g., n.sp. is described from the pangolin Manis pentadactyla in India. Both parasitic free-living generations have been examined. Features which differentiate the parasite from Strongyloides and Parastrongyloides are described.


Genus Microsporum dermatophytes in Eastern Bohemia. The authors presented a taxonomic survey of dermatophytes of the genus Microsporum. From the 19 species described so far, they isolated ten species in the region of Eastern Bohemia. Only the species Microsporum cookei and M. gypsem are considered to be endemic species. The remaining are regarded as imported dermatophytes which are not able to maintain their existence permanently in the conditions of the mentioned region. Data on the findings of the individual species were completed by the authors' remarks on their primary hosts and/or substrates of heterotrophy, frequency of occurrence and geographical distribution.


Residual disinfection of some preparations and substances. The results of our experiments over many years point to the possibility of practical application of disinfectants of residual effect. In our opinion, further investigations should be carried out in the following two directions: detection of new means and preparations showing uniform properties and development of an optimum method of their application. We believe that residual disinfection will play a role in the prophylaxis of hospitalism.


Taxonomy of the family Vibrionaceae considered with respect to data on the primary structure of deoxyribonucleic acid.


Human infections caused by V. parahaemolyticus in Czechoslovakia. Vibrio parahaemolyticus was isolated in two subjects with acute gastroenteritis. The patients' history included stay in Pakistan or India. They probably contracted the infection on board an aeroplane where they ingested cold meal containing sea products. The possibility of this conditioned pathogen occurring also in an inland country is pointed out.


Nephelometric density adjustment of leptospiral antigen. In testing leptospirosis by microagglutination, reproducibility of the results is affected by population age and germ concentration. These undersirable factors can be avoided if antibody identification is made with cultures incubated for 7 to 21 days and adjusted to 50 X 10(6) leptospires per millilitre. Most suitable for the purpose is an analogue mode based on nephelometry and the probability theory. The obtained statistical data furnish calculated and tabulated apparatus values which are used for standardizing with the aid of a newly developed nepheloflask with compression-spring stirrer.


Diurnal variation and the episodic release of plasma gonadotrophins in Japanese quail during a photoperiodically induced gonadal cycle. Blood samples were taken every 3 h, over a 27 h period, from (1) a group of 12 intact male quail on short days (lights on 09.00-17.00 h) and during the 2nd, 15th and 36th day of photostimulation (lights on 09.00-05.00 h); (2) 12 castrated male quail on the 2nd, 20th and 43rd long day, and (3) 12 intact male quail on the 12th long day. Plasma LH was measured in all samples and FSH in the 43rd long day castrate and 12th long day intact male samples. Although there was considerable variation in the levels of LH and FSH, both between birds and between samples taken from the same bird, statistical analyses failed to reveal any diurnal (or circadian) rhythm at any time. There was a marked correlation between the LH and FSH levels in all samples. Possible episodic LH secretion was investigated by taking blood samples every 15 min for between 3 and 6 h from six intact male quail and six laying females on long days. Samples were obtained from each bird at three time-periods which were arranged so as to overlap and cover the first 12 h of the daily photoperiod. Statistical analysis suggested that episodes of secretion occurred 6-10 times/day in males, and 4-8 times/day in females. The pulses appeared to occur at random.


Influence of 16-aryloxyprostaglandins on the production of progesterone by human granulosa cells in vitro. 16-Aryloxy analogues of prostaglandin F2alpha (PGF2alpha) are potent luteolysins in laboratory and farm animals. When their effect on progesterone production by luteinized human granulosa cells in tissue culture was investigated inhibition of both basal gonadotrophin-stimulated progesterone production was observed, so revealing characteristics expected of potential human luteolysins. The analogues were, however, unable to inhibit progesterone production stimulated by PGE2, suggesting that like PGF2alpha these compounds may act by specifically blocking LH-activated adenylate cyclase. The 16-aryloxyprostaglandins similarly inhibited progesterone production by porcine granulosa cells, so that the effects observed with the 16-aryloxyprostaglandins in vitro may be indicative of their potential in vivo.


Surviving trophoblastic giant cells and ovarian function after prostaglandin-induced abortion in the golden hamster.


Diurnal variation in the activity of hepatic glycerol-3-phosphate acyltransferase in response to ovine prolactin in goldfish, Carassius auratus L.


Cell patterning in migrating slugs of Dictyostelium discoideum. When front quarters of migrating slugs of Dictyostelium discoideum are isolated by surgery and induced to friut immediately they produce fruiting bodies with disproportionately large stalks (Raper, 1940). The data in this communication show that the 'stalky' character of fruits derived from front quarters persists even if the cells of the front quarter are disaggregated and hence to reaggregate before fruiting. The data also demonstrate that friuts derived from rear quarters of slugs have disproportionately large spore heads, and that this effect becomes more pronounced with increasing age of the slugs. These observations support the view that the cells of the front and rear of migrating slugs are to some extent committed to different fates.


Direct exposure of postimplantation mouse embryos to 5-bromodeoxyuridine in vitro and its effect on subsequent chondrogenesis in the limbs. As maternally administered 5-bromodeoxyuridine (BudR) is very quickly degraded by the liver, a combination of whole embryo culture and organ culture techniques was adopted to expose postimplantation mouse embryos to the analog and to study the effects of long-term embryos were exposed to increasing concentrations of BudR for 12 or 24 h. Forelimbs of the treated embryos were then organ-cultured in drug-free medium and the extent of cartilage development in the explants examined. Exposure of embryos to 50-150 mug/ml of BudR for 24 h resulted in significant inhibition of chondrogenesis in the subsequent limb cultures and the effect was related to dose. After treatment with 150 mug/ml of the drug, the forelimbs of the early 11-day embryos (somite stage 26-29) showed an almost complete lack of cartilage, while the limbs of mid-11 th-day embryos (somite stage 32-34) were not nearly as sensitive and exhibited about 50% reduction in the amount of cartilage development. We conclude that if embryos in which the limb development is at a very early stage of development are exposed to BudR, the future course of limb differentiation is permanently and irreversibly damaged, resulting in a partial or even complete suppression of chondrogenesis in the organ. As both the dose and perhaps also the duration of treatment were critical, we suggest that the rather low frequency of reported limb malformations after in vivo injection of teratological doses of BudR may be due to only a small amount of the chemical reaching the embryos.


Nuclei, septation, branching and growth of Geotrichum candidum. A study was made of growth, septation and branching in Geotrichum candidum, a mould which forms physiologically complete septa. A correlation was observed between septation and branch initiation; branches were almost invariably formed just behind septa. Primary branches and their parent intercalary compartments initially increased in length at an exponential rate before eventually attaining a constant rate of extension. The whole branching system (which eventually contained seven tips) produced by an intercalary compartment increased in length exponentially until it attained a total length of at least 1-5 mm. The total length and the number of nuclei of undifferentiated mycelia increased exponentially at the same specific growth rate. The results suggest that nuclei divide just before or just after arthrospore formation.


The relationship between the uptake of glucose and 3-O-methylglucose and soluble carbohydrate and polysaccharide in the fungus Dendryphiella salina. When mycelium of Dendryphiella salina, pre-incubated in D-[I-14C]mannitol such that this is the only major labelled soluble carbohydrate present, absorbs glucose or the non-metabolized sugar 3-O-methylglucose, there is a specific stimulation of incorporation of 14C into alkali-insoluble, trichloroacetic-acid-soluble (1 leads to 4)-alpha-glucan, probably glycogen. There is also a net increase in the amount of glucan caused by stimulation of synthesis and inhibition of breakdown. Addition of 3-O-methylglucose results in the loss of mannitol into the medium. This loss and the reduced rate of replenishment from the glucan is important in the osmotic regulation of the hyphae. If osmotic adjustment does not occur, the hyphae do not show the specific incorporation of 14C into the glucan.


Isolation of 4-ribitylamino-5-amino-2,6-dihydroxypyrimidine from a high flavinogenic mold Eremothecium ashbyii1. The addition of glyoxal, a trapping agent, caused simultaneously the accumulation of a green fluorescent compound and the inhibition of riboflavin formation in non-growing cells of Eremothecium ashbyii. The fluorescent compound purified was identified as 8-ribityllumazine from the results of spectrophotometric and fluorometric analyses. Accordingly, the fragment, except for the glyoxal portion on the 8-ribityllumazine molecule, 4-ribitylamino-5-amino-2,6-dihydroxypyrimidine, is believed to be an intermediate in the riboflavin biosynthetic pathway.


A chemically-defined medium for the growth of a ureolytic strain of Streptococcus faecium. A chemically-defined medium was developed which supported growth of Streptococcus faecium and permitted synthesis of urease. This streptococcus cannot utilize ammonia and needs a complex medium, but its requirements are probably provided in the rumen. The specific activity of urease was inversely related to growth and in no medium was there high growth and high urease activity. Anaerobic culture and the presence of urea in the medium were essential for urease activity, but not for growth.


Occurrence of familial spastic paraplegia in only one of monozygous twins. Three patients who suffer from spastic paraplegia are described who belong to two generations in one family. One of the patients, who has had symptoms and signs for at least 10 years, has a monozygous twin who is unaffected. Using blood groups and chromosomal polymorphisms, the probability of monozygosity is estimated to be 0.99986. The observation of nonpenetrance in familial spastic paraplegia suggests that environmental factors may be involved in provocation and emphasises the need for careful genetic counselling in this and related diseases.


Identification of the second product of the riboflavin synthetase reaction. This study was concerned with the detailed identification of the second product involved in the riboflavin synthetase reaction with riboflavin synthetase from Eremothecium ashbyii and a trapping agent, glyoxal.Thus, a green fluorescent compound accumulated during the incubation. The compound was purified through various column chromatography steps, and was examined by UV, IR, excitation and emission spectra and paper chromatography to prove that the isolated compound was 8-ribityllumazine. Accordingly it was concluded that a second product in riboflavin synthetase reaction was 4-ribitylamino-5-amino-2,6-dihydroxypyrimidine, the fragment, except for C-6 and C-7 of 8-ribityllumazine, being an incorporated glyoxal portion.


Competition between some neutral amino acids for carrier-mediated transport into the brain in vivo [proceedings].


Electrical excitability of cultured adrenal chromaffin cells. 1. Adult human and gerbil adrenal medullary cells were maintained in dissociated cell culture and studied by micro-electrode penetration. 2. In the best recordings, chromaffin cell transmembrane potentials exceeded -50mV. 3. Chromaffin cells were capable of generating all-or-nothing over-shooting action potentials, similar to those generated by sympathetic neurones. 4. The action potentials were blocked by tetrodotoxin (TTX, 10(-6)g/ml.) but were not blocked by removal of Ca or by CoCl2 (10 mM). We conclude that the action potentials are probably generated by a Na mechanism. 5. Chromaffin cells are depolarized by the iontophoretic application of acetylcholine (ACh). This depolarization was accompanied by an increased membrane conductance and could trigger action potentials. 6. Action potentials were also found in cells in fresh slices of gerbil adrenal medullae.


Control of blood pressure oscillation elicited by bleeding. 1) A control objective regarding the blood pressure oscillation is to decrease the heart rate. 2) The transfusion of a small amount of blood at the bottom of a cycle in the oscillation is usually useful as a control plan for the blood pressure oscillation. 3) A partial occlusion of the abdominal aorta is effective in arresting the oscillation, but the oscillation starts again after releasing the abdominal aorta from the partial occlusion.


Separation technique of phase-locked and -unlocked spikes to the vibratory stimulation in the tonic vibration reflex.


Androgens and male sexual function: a review of human studies. The scope of this article will be a review and brief discussion of recently gathered information on androgens and sexual behavior in men. It will include experimental observations on the covariance between androgens, mainly testosterone, and sexual functioning in normal heterosexual men and studies on sexual dysfunction and homo-sexual behavior. The effects of castration, hypogonadal conditions, hormonal replacement, and endogenous testosterone variations on sexual behavior are examined. Further psychoendocrine studies, are necessary to evaluate the role of gonadal hormone production in impotency. Current pharmacological research does not furnish specific evidence, that the administration of androgens or preparations that stimulate the secretion of endogenous androgens have beneficial effects on functional impotence. After reviewing the studies on male homosexuality and androgen levels, the article concludes that it has not been established that homosexual men are characterized by abnormalities in plasma testosterone.


Issues in the use of psychophysiology to assess female sexual dysfunction. The viability of psychophysiology as an assessment approach for female sexual function and dysfunction revolves around physiological measurement issues, subjective measurement issues, and the nature of the sexual difficulty. Recent data are presented and discussed as are the potentials and limitations inherent in a psychophysiological study of human sexuality. A case is made for the use of vaginal pressure pulse as a primary measure, vaginal blood volume as a secondary measure, correlations between subjective and objective measures of sexual arousal, and intercorrelations between various subjective affect scales.


Preparation of cultured cells for SEM: air drying from organic solvents. Air evaporation from organic solvents of differing polarities and surface free energies was used in the preparation of cultured murine peritoneal macrophages for scanning electron microscopy (SEM). The surface structural features of these cells were compared to the surfaces of similar cells prepared by the critical-point procedure. In general, all organic solvents produced a marked collapse of cell structure resulting in an increase in surface irregularity. Fracture surfaces and sharply defined contours including numerous flaps and ridges were characteristic of the non-polar solvent dehydrated samples. Polar solvent dehydrated samples, including those dried from solvents of low surface free energy, exhibited a secondary flowing and settling of the cell membrane. Primary collapse was apparent but cell contours were smoothed and rounded. Overall cell shape and cell-to-cell relationships were retained regardless of solvent type. It is suggested that solvent evaporation may prove useful in certain cases, though investigators are advised to use caution when interpreting the results obtained by such procedures.


Heterogeneity of spacer lengths in circles of amplified ribosomal DNA of two insect species, Dytiscus marginalis and Acheta domesticus.


Isolation of Monosporium apiospermum from cerebrospinal fluid.


A beta-adrenergic stimulant, salbutamol, in the treatment of pertussis.


Experimental gastric ulcers in the fundic gland area following transplantation of the gastric-wall pedicles. Using adult mongrel dogs, a portion of the anterior gastric wall of the pyloric gland area was transplanted into the fundic gland area using the Z-plastic procedure forming an islet. Three weeks postoperatively, 2 per cent histamine in sesame oil was injected intramuscularly in a daily dose of 2 mg/kg body weight. Ulcers developed in the graft in nine of 19 animals. The factors responsible to the development of the ulcers may well be circulatory disturbance and reduction of mucosal resistance following surgical insult, and continuous irritation caused by gastric juice. When a portion of the anterior gastric wall of the fundic gland area was transplanted into the fundic gland area followed by administration of histamine in sesame oil, ulcers developed in the graft only in four of 12 animals. Histological examination revealed the regenerated epithelium at the margin of the ulcers. Thus the ulcers presently induced may provide an useful experimental model for ulcers in the fundic gland area.


Studies on Yersinia pseudotuberculosis. IV. Isolation of Y. pseudotuberculosis from healthy swine.


Clinical and pathological studies on a spontaneous case of canine systemic atrophic myositis.


Delayed hypersensitivity responses of guinea pig and rat to Angiostrongylus cantonensis infection.


The gastric venous system of the domestic goose.


Cadmium-binding protein in tissues of male rats and Japanese quail.


Bacteriophage typing of Staphylococcus aureus isolated from chicken staphylococcosis in Japan.


A device for detection of heat in heat-silent buffaloes.


Genetic marker in beagle blood: individual difference within blood groups detected by isohemagglutinin.


Malignant haemangioendothelioma (angiosarcoma) in the dog.


Spontaneous neoplasms of the central nervous system of the cat.


Estradiol receptors: influence of plasma proteins on detection and quantitation.


A radioimmunoassay for betamethazone. Preparation of a specific antiserum to betamethazone-3 (O-carboxymethyl) oxime-bovine serum albumin and evaluation of method.


Application of theoretical models in ecology.


Experimental investigations on the different hepatotoxic potential of erythromycin derivatives.


Trypsin and chymotrypsin inhibitors from soybeans.


Effect of certain nitrogenous heterocyclic compounds on carotenogenesis in Verticillium agaricinum. Pyridine, isonicotinoylhydrazide and 1-methylamidazole have been used to investigate carotenoid biosynthesis in V. agaricinum. The results suggest that both torulin (C40) and neurosporaxanthin (C35) are formed from the precursors phytoene and phytofluene. These was no evidence of lycopene accumulation under these conditions. After 4 days' growth in the presence of isocotinolyhydrazine the fungus contained torulin and neurosporaxanthin only, whereas after 7 days, seven other carotenoids appeared as well, some of which were at the early stages of carotenoid biosynthesis. There results cannot be explained on the basis of a system consisting of free enzymes but of an enzyme aggregate already proposed for Phycomyces.


Studies of pharmacological activity several acridine derivatives with cytostatic and oncostatic properties.


Mycobacterium marinum infection from a tropical fish tank. Treatment with trimethoprim and sulphamethoxazole. A paronychial granuloma on the left thumb, in a man who kept tanks of tropical fish, was followed by cutaneous nodules on the left upper limb and tender lymph nodes in the left axilla. Mycobacterium marinum was isolated from the lesion on the thumb and also from the tank water. Subsidence of the lesions followed administration of trimethoprim and sulphamethoxazole.


Behavior of some biochemical components of blood of patients with ovarian carcinoma during Ledakrin treatment.


Antineoplastic activity of C-283 preparation (Ledakrin) in model experiments.


Isolation and characterization of compatible diploids of Schizophyllum commune. Common-AB diploids with several heterozygous biochemical markers were mated with appropriately marked haploid strains of S. commune in an effort to obtain compatible, common-A, and common-B diploid progeny with biochemical markers identical to those of the common-AB parent. The spores from these crosses were germinated on minimal medium. Five compatible diploids, but no common-A or common-B diploids, marked as desired, were isolated by this method. Two possessed some dikaryotic cells and two had many dikaryotic cells. One of the latter was shown to have peculiar behaviour associated with one of its B mating-type factors.


The dominant lethal effect of dietary triethylenemelamine. Triethylenemelamine (TEM) was administered in the diet to adult male mice at doses of 0.1, 0.3, 1, 10 or 50 mg/kg body weight for 45 days or at doses of 0.1 or 0.3 mg/kg b.w. for 10 days. As a comparison, male mice were treated intraperitoneally with 5 daily doses of 0.25 or 0.5 mg TEM/kg b.w. At the end of the treatment period, males were mated sequentially with 2 untreated virgin females each for 2 or 3 weeks. Near mid-pregnancy the number of implantation sites and fetal deaths were determined. TEM, administered in the diet at 10 or 50 mg/kg b.w. for 45 dyas, was lethal to male mice. Surviving males from the 1 mg/kg level failed to impregnate any females during the two matings. TEM, given in the diet at 0.1 or 0.3 mg/kg for 10 or 45 dyas, decreased fertility and increased dominant lethal mutations in a dose and time dependent manner. These results were comparable to those obtained from males treated i.p. with TEM at 0.25 or 0.5 mg/kg b.w.


Production of immunoglobulins by tumor cell lines from avian lymphoid leukosis. Two avian lymphoma cell lines, 1104-X-5 and 1104-B, were examined for ability to produce immunoglobulin. They were found to produce and release the components of immunoglobulins related to IgG and IgM. The analysis of sucrose density gradient and gel electrophoresis suggested that these components might consist of light chains and fragments of heavy chains.


Activity of the nigro-striatal dopaminergic system during precipitated morphine withdrawal investigated in rats with acute unilateral inactivation of the striatum. The activity of the striatal dopamine system during precipitated morphine withdrawl was studied in rats using a model in which the striatum was unilaterally inactivated by the local injection of KCl. In naive rats dopamine agonists administered just prior to KCL induced ipsilateral turning or circling, while dopamine antagonists in the same situation caused contralateral turning. Withdrawal precipitated by morphine antagonists in rats made dependent by repeated implantation of morphine pellets induced contralateral circling during unilateral inactivation of the striatum. This contralateral circling was only slightly enhanced by haloperidol, but strongly enhanced by a low dosage of apomorphine as well as by some weak dopamine agonists such as CB 154 or By 101. However, high doses of apomorphine completely reversed the withdrawal-induced contralateral circling into ipsilateral circling. Other dopamine agonists, such as d-amphetamine, L-Dopa and piribedil, did not abolish the withdrawal-induced contralateral circling, however, they caused the appearance of an additional ipsilateral circling. Other types of drugs which are known to intensify withdrawal-induced jumping (desipramine, atropine, caffeine) enhanced contralateral circling. There are also other parallels jumping and contralateral circling induced by withdrawal. The direction of naloxone-induced asymmetric behaviour during acute unilateral inactivation of the striatum suggests that striatal dopaminergic activity is reduced during precipitated withdrawal; the other results reported point to the possiblity that extrastriatal dopaminergic mechanisms or different dopamine receptor types within the striatum are involved.


Description and chemical analysis of a new species of hallucinogenic Psilocybe from the Pacific Northwest.


Re-analysis of radiation-induced specific locus mutations in the mouse. A re-analysis of published data on mouse mutation rates induced by X and gamma rays suggests that the kinetics of induction can be analysed by fitting the data to a parabolic curve. We interpret this to mean that a substantial proportion of the induced mutations results from gross chromosomal changes such as deletions, some of which are one-track and some of which are two-track. This analysis is based on the assumption that the shape of the dose curve, which in the female is concave upward, reflects the manner in which the mutations are induced rather than representing a one-track (linear) curve whose shape has been modified by differential repair.


Psychotropic mycoflora of Washington, Idaho, Oregon, California and British Columbia.


Progesterone action on estrous rhythm in the rat following ventromedial nucleus lesions. Small bilateral lesions of the hypothalamic ventromedial nucleus (SVMN) were produced in 4 day cyclic female Wistar rats by passing a 2 mA cathodic current through stereotaxically oriented platinum unipolar electrodes for 7 sec. The 24 h lengthening of cycle which occurred in 111 our ot 208 females was shown to depend upon lesion placement. Early s.c. injection of 0.75 or 1.5 mg progesterone caused 24 h cycle prolongation more frequently in SVMN-lesioned females with maintained 4 day cycles than in 4 day cyclic unoperated, sham VMN-lesioned, or dorsomedial nucleus (DMN) lesioned females. This effect proved to be related to lesion placement. It was therefore concluded that the VMN is involved in the mechanisms whereby progesterone controls estrous cycle duration in the rat.


The contribution of genetics to biological psychiatry. One of the most striking developments in the framework of biological psychiatry, is the use of human as well as animal genetics' methodology in psychiatric research. After reviewing some basic concepts in human genetic research, we shall present the current status of our knowledge on the genetic determinants of the major psychoses, i.e., the affective psychoses and schizophrenia. The importance of genetic research into psychiatry can also be underscored from a biometric point of view in showing its contribution to the clarification of problem of nosology in attempting to subclassify abnormal behavior on a more etiological basis. Finally, a still open field essential to our comprehension of therapeutics emerges from the study of genetic mechanisms involved in drug metabolism and drug response.


Aortic prolyl hydroxylase and the development of arteriosclerosis in the female breeder rat. Female breeder rats develop arteriosclerosis spontaneously. The primary lesions seen in the early stages of the disease consist of subintimal and adjacent medial ground substance accumulations. With repeated breeding there is extensive elastolysis and calcification in the aorta. In aortae with developing arterial disease, prolyl hydroxylase activity is elevated as is both aortic protein and hydroxyproline, indicative of increased collagen deposition associated with the sclerotic degeneration. As the disease becomes very severe, however, prolyl hydroxylase activity declines, possibly associated with decreased metabolic activity in the severely calcified aorta. Lactation, followed by forced weaning, may condition the development or arterial disease through effect on collagen metabolism. During the first breeding cycle, aortic prolyl hydroxylase activity is elevated for 5 to 10 days after weaning. This increased collagen metabolism in the aorta may be a primary event in the development of the advanced calcific lesions characteristic of the lesions in breeder rats, and may be affected by hormones associated with different phases of the reproductive cycle.


The M. omohyoideus of the mouse as a convenient mammalian muscle preparation.  A study of junctional and extrajunctional acetylcholine receptors by noise analysis and cooperativity. Muscles from cats, rats, guinea pigs and mice have been investigated as preparations for visualizing mammalian neuromuscular junctions with the aid of Nomarski interference optics. The M. omohyoideus of the mouse was found to be most convenient. Electrophysiological investigations showed that an endplate is normally surrounded by a population of perijunctional receptors. For junctional receptors in the endplate, a Hill coefficient of nH = 2.6 for acetylcholine was determined at 38 degrees C, decreasing to a value of 2.3 at room temperature. For both perijunctional and extrajunctional receptors (the latter occurring after denervation), the coefficient nH was 1.9. Noise analysis revealed a channel conductance gamma which changed abruptly from 22.4 +/- 1.0 pS (10--23 degrees C) to 45.6 +/- 3.9 pS (34--39 degrees C) in a very small temperature range around 25.5 degrees C. The mean channel lifetime tau was 0.3 ms at 39 degrees C and 1.0 ms at 23 degrees C.


Renal tubular reabsorption of taurine, gamma-aminobutyric acid (GABA) and beta-alanine studied by continuous microperfusion. Renal tubular reabsorption of taurine, gamma-aminobutyric acid (GABA), and beta-alanine was studied in vivo et situ by continuous microperfusion of single proximal tubules of the rat. In each case, reabsorption was much slower than that for other amino acids that have been studied. With a concentration of 0.1 mmol/l in initial load was reabsorbed over perfusion distance of 3 mm. Taurine reabsorption saturated with only 2.17 mmol/l in initial perfusate. Assuming simple two-parameter kinetics, upper limits for Km of 0.54 mmol/l and forVmax of 0.59 pmol-cm-1--s-1 for tubular reabsorption of taurine were estimated. High (20 mmol/l) concentrations of taurine or beta-alanine in perfusate completely inhibited GABA reabsorption, but L-phenylalanine (20 mmol/l) had no significant effect. The results indicate that the three amino acids are reabsorbed slowly from the proximal tubule by what may be a common transport system. This system appears to have a high affinity but low capacity and to be different from other known renal tubular transport systems for amino acids.


The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. The time course of phosphorylcreatine (PC) resynthesis in the human m. quadriceps femoris was studied during recovery from exhaustive dynamic exercise and from isometric contraction sustained to fatigue. The immediate postexercise muscle PC content after either form of exercise was 15-16% of the resting muscle content. The time course of PC resynthesis during recovery was biphasic exhibiting a fast and slow recovery component. The half-time for the fast component was 21-22s but this accounted for a smaller fraction of the total PC restored during recovery from the isometric contraction than after the dynamic exercise. The half-time for the slow component was in each case more than 170 s. After 2 and 4 min recovery the total amount of PC resynthesized after the isometric exercise were significantly lower than from the dynamic exercise. Occlusion of the circulation of the quadriceps completely abolished the resynthesis of PC. Restoration of resynthesis occurred only after release of occlusion.


Elimination of vasopressin by the normal and the damaged liver. Experiments on unanaesthetized normal and thiocetamide treated rats with a note on the influence of ethanol. Arginine vasopressin was infused into the V. portae and into the V. cava of unanesthetized rats in water diuresis. The differential antidiuretic response of the same animal to these infusions was used to calculate extraction fraction of ADH by the liver. In the normal rat no extraction was detected. The liver of rats hydrated with 5% ethanol extracted 10% and that of rats treated with thioacetamide extracted 60% of the ADH infused into the portal vein. It is postulated that disturbances of liver cell function by narcotics and substances causing liver damage may liberate ADH-destroying ferments into the blood.


Evaluation of a neurogenic rapid coronary dilatation during an excitatory response in conscious dogs. The present study was undertaken to evaluate the mechanisms of coronary adaptation to sudden changes in myocardial oxygen demand that occur during excitement. An excitatory response was evoked either by electrical stimulation of the hypothalamic defence area or by noise (discharge of a fire-arm). Continuous measurement of the oxygen saturation in coronary venous blood was used to judge, whether an increase in coronary flow was adequate to match an increased myocardial oxygen demand. During the excitatory response heart rate, cardiac output and coronary flow increased. However, the increase in coronary flow was not adequate to meet the increased metabolic requirement as indicated by a decrease in coronary venous oxygen saturation. In dogs with experimental atrioventricular block, and with heart rate controlled by external pacing, a rapid coronary dilation occurred during the excitatory response and was accompanied by an increase in coronary venous oxygen saturation. This rapid coronary dilation was abolished by beta-adrenergic blockade. The pattern of coronary flow and coronary venous oxygen saturation that occurred during the excitatory response in normal dogs could be mimicked in dogs with atrioventricular block by increasing the ventricular pacing rate. However, when identical increases in heart rate were induced either excitement or by external pacing, the drop in coronary venous oxygen saturation was significantly larger in the paced series. This demonstrates, that an increase in heart rate is responsible for the transient decrease in coronary venous oxygen saturation during the excitatory response. From these experiments it is concluded that a rapid neurogenic dilation of the coronary vessels occurs during the excitatory response. Under normal conditions this rapid neurogenic dilation is masked by the effect of the accompanying increase in heart rate on extravascular coronary resistance.


Renal urate transport during variations in urate synthesis in the rat. In order to determine the effect of intrarenal synthesis of urate upon the urinary urate excretion in the rat, we effected large changes in urate synthesis by increasing it with allopurinol. Hypoxanthine infusion increased plasma urate rapidly and also increased the urinary urate excretion and its renal clearance. However, when the plasma urate was maintained constant, hypoxanthine had no effect upon renal urate transport. Conversely, allpurinol infusion rapidly diminished the plasma urate, urinary urate excretion and its renal clearance. Again, the maintenance of a constant plasma urate concentration prevented any change in urate transport during allopurinol. The urinary degradative purine metabolic pattern was altered predictably by hypoxanthine and allopurinol. Assuming than any putative intrarenal component of urate synthesis would be affected predictably and consistently by hypoxanthine and allopurinol, these results suggest that changes in intrarenal urate synthesis are not an important determinant of urate excretion in the rat.


Effects of saline loading on jejunal absorption of calcium, sodium, and water, and on parathyroid hormone secretion in the rat. To investigate whether intestinal calcium absorption parallels that of sodium following extra-cellular fluid volume expansion, the effects of saline loading on intestinal transport of calcium, sodium and water were studied in rats by perfusing jejunal loops in situ. After calcium-free saline infusion net calcium absorption was reversed similar to that of sodium and water and net secretion occurred. Concurrently, blood-to-lumen (b-l) calcium flux, measured using 45Ca, increased significantly (P less than 0.001). Following expansion with calcium-containing Ringer a similar reversal of net calcium, sodium and water flux was also observed. Again the b-l calicum flux increased but to a significantly lesser extent (P less than 0.05). Plasma ionized calcium remained unchanged after calcium-rich Ringer loading, but decreased significantly (P less than 0.001) when calcium was omitted from the solution. Plasma immunoreactive parathyroid hormone unchanged after expansion with the calcium containing solution but increased following calcum-free infusion. It is concluded that after extracellular fluid volume expansion: 1. net jejunal calcium absorption is decreased; 2. the decrease parallels that of sodium and water; 3. b-l calcium transport is enhanced to a greater degree of calcium-free Rnger infusion than by a calcium-rich solution. This difference could be the result of increased parathyroid hormone secretion.


A continuous-flow, variable mixing valve for perfusion experiments. The device described here continuously mixes two solutions in any required ratio and has been used at flow rates of 6 ml/min in tissue perfusion experiments. Its low-cost construction consists of a three-way miniature solenoid valve driven by a simple electronic circuit. Mixing is stable, reproducible and accurate to +/- 1% of dial setting.


Fatigue and caffeine effects in fast-twitch and slow-twitch muscles of the mouse. In excised, curarized and massively stimulated fast-twitch mouse gastrocnemius muscles the early twitch tension enhancements (treppe) during 1/s activity between 10 and 36 degrees C increase and affect more contractions as temperature increases. Tension output eventually declines at a temperature-independent rate. Half-relaxation time lengthens below 25 degrees C and shortens above 25 degrees C. During 1/0.63s twitches half-relaxation time lengthens even at 25 degrees C. In slow-twitch soleus muscles activity decreases twitch tension and half-relaxation time regardless of temperature. Activity shortens contraction times in both muscles. Oxygen lack induced by NaN3 cannot account satisfactorily for these results. Activation is apparently more plastic in the gastrocnemius than in the soleus, and the relationship between the rates of their activation and relaxation processes and the temperature sensitivities of these rates also seem to differ. In both muscles caffeine can convert activity-induced shortened of half-relaxation times into prolongations. In the soleus this effect is more pronounced at 30 than at 25 degrees C. At high temperature and twitch rates caffeine reduces treppe amplitude and duration without affecting the eventual twitch tension decline in the gastrocnemius while it greatly accelerates twitch tension decline in the soleus. In both muscles intrafiber Ca2+ movements are apparently major determinants of fatigue behavior.


Prophylactic, postinfectious and neonatal vaccination against canine distemper in mink. Mink were vaccinated against canine distemper and challenged with the Snyder Hill strain of canine distemper virus. Protection was acquired if vaccination took place more than a few days before challenge. If vaccination took place even early during incubation mortality was higher than in the unvaccinated controls. Full protection of kits may be achieved even at an age of 16 to 20 days provided the kits had not passively acquired immunity from their mothers. Kits surviving distemper because of passively acquired immunity may not actively acquire immunity during infection and may die at a later exposure.


Hypertension in pregnancy.

Hypertension in pregnancy.


Clinical applications of 24 hour electrocardiogram recordings.


Spectrum of pharmacological actions on brain dopamine. Indications for development of new psychoactive drugs. Discussion of amantadines as examples of new drugs with special actions on dopamine systems. Amantadine (D1) and 1,3-dimethyl-5-aminoadamantane (D145) as examples of new drugs with special actions on dopamine systems are discussed. D1 or D145 decreased significantly apomorphine or amphetamine-induced stereotypy in rats but in experiments with chronic pretreatment with amantadines -- potentiation of stereotypy was observed. D145 (20 mg/kg) abolished stereotypy in these conditions. In biochemical experiments D1 or D145 were neither like apomorphine nor like amphetamine. Its concluded that D1 and D145 in addition to their amine releasing properties have the ability partially to occupy the dopaminergic receptor.


Central action of ergometrine.

Central action of ergometrine. Ergometrine, a spasmolytic which also stimulates dopamine receptors, was investigated as a potential central stimulant. It did not influence the locomotor activity of normal rats and mice, and in high doses even depressed it. The locomotor activity depressed by reserpine, spiroperidol, and pimozide was elevated by ergometrine. Ergometrine antagonized neuroleptic-induced catalepsy and abolished ptosis and hypothermia produced by reserpine. Given alone ergometrine depressed the body temperature in rats and mice, and this effect was abolished by pimozide in both species, and by spiroperidol and haloperidol in mice. The hypothermia was not antagonized by atropine. In several respects the central action of ergometrine resembles that of apomorphine.


The effect of theophylline and caffeine on neuroleptic-induced catalepsy.


Tissue culture of rat lenses.

Tissue culture of rat lenses.


Effects of pyrazolone-5 derivatives on amphetamine-induced hyperthermia and behavioural changes in rats.


Effect of angiotensin on the central action of dopamine. Angiotensin given intraventricularly enhances amphetamine but not apomorphine-induced stereotypy 30 min. after peptide administration. Simultaneous injection of angiotensin and dopamine increases amphetamine -- while decreases apomorphine -- induced stereotypy. The stereotypy produced either by apomorphine or amphetamine in rats pretreated with Ro 4-4602 + L-DOPA was diminished by angiotensin. Angiotensin elevated haloperidol-induced catalepsy. A possibility that angiotensin may inhibit both release and uptake of dopamine by nerve endings is discussed.


Effect of pinealectomy and of bilateral cervical ganglionectomy on serum LH levels in constant estrous-anovulatory rats. The effects of pinealectomy or bilateral superior cervical ganglionectomy on serum luteinizing hormone (LH) levels and ovulation were studied in constant estrous-anovulatory rats bearing a frontal hypothalamic deafferentation (FHD).  Ovulation returned in 65% of the animals undergoing pinealectomy or bilateral superior cervical ganglionectomy.  Almost 50% of these ovulating animals showed elevated serum levels of LH on the day of vaginal proestrus, while the remainder ovulated without appreciable changes in serum LH concentrations.  It is suggested that the absence of an LH peak in the latter cases was due to an insufficient sampling size.  The results suggest that pinealectomy and cervical sympathectomy may result in LH release by interference with the hypothalamic and brain stem serotonergic system involved in the inhibition of LH release.


Inhibition of interferon action by cytochalasin B, colchicine, and vinblastine.


Interferon assay of high sensitivity.

Interferon assay of high sensitivity.


Influence of albumin degradation products (ADP) on the central action of catecholamines. The influence of ADP on the central action of catecholamines was investigated. ADP abolished the central action of noradrenaline, amphetamine and nialamide. The peptides decreased apomorphine stereotypy and enhanced haloperidol induced catalepsy. These results support our previous suggestions [10-14] that ADP acts on the CNS by antagonizing the action of central catecholamines.


The effect of bradykinin on central dopamine receptors. Bradykinin (BK) injected intraventricularly (ivc) at doses of 0.25-0.5 mug per rat potentiated the depth of fluphenazine catalepsy and depressed or abolished the symptoms of sterotypy produced by amphetamine or apomorphine. BK did not affect the level of dopamine (DA), but elevated the level of homovanillic acid in the brain, and accelerated DA turnover as measured by the rate of dopamine disappearance following treatment with alpha-methyltyrosine. The results suggest that BK inhibits the central dopamine structures by blocking the DA receptors.


Hormones and regional brain blood flow.

Hormones and regional brain blood flow. Acute effects of the hormones, estradiol-17beta and alphaMSH, and of neonatal pretreatment with alphaMSH on the flow of blood to regions of the brains of conscious adult rats have been determined with an indicator distribution technique. As previously reported, flows were reduced in most areas within 10 min after intravenous administration of alphaMSH; only the occipital cortex was spared. Though these effects were transitroy for most areas, perfusion of pons and medulla, cerebellum, hippocampus and parietal cortex was still low by 20 min. However, pretreatment with alphaMSH during infancy led to persistent behavioral changes which were not accompanied by flow differences. Assuming that flow changes reflect functional changes, the rapid responses to alphaMSH suggest an explanation for the effects of this hormone on visual learning and on the determination of subsequent learning behavior. By contrast, estradiol, within 10 min after injection, increased flow to most regions of the brain, especially the frontal cortex, hippocampus, basal ganglia and cerebellum; females were more affected than males. Flow changes were greater than those elicited by more obvious behavior-modifying drugs. Compared to alphaMSH, the flow data for estradiol suggest a physiologic basis for a behavioral effect which is likely to be different yet, perhaps, equally profound.


Effects of monoolein on hydrolysis of triglyceride by lipoprotein lipase in the presence of an inhibitory apolipoprotein. The previously demonstrated inhibition of cow's milk lipoprotein lipase by apoLp-Ala and the deinhibition by monoglyceride have been studied in more detail. The apoLp-Ala inhibition is reversible by the addition of monoglyceride before or after enzyme additions. Quantities of monoglyceride accumulate during hydrolysis of triglyceride which are adequate to prevent inhibition by added apoLp-Ala. Accelerating reaction rates observed when the substrate contains the apoprotein at levels producing partial inhibition are also explained by monoglyceride production. These effects were observed with both crude preparations of skim milk and highly pruified lipase. It is suggested that the generation of monoglyceride may be important in facilitating hydrolysis of triglyceride in lipoproteins containing this inhibitory apolipoprotein.


Gonadal hormones and body temperature in rats: effects of estrous cycles, castration and steroid replacement.


Hexobarbital sleeping time in the rat: effects of isolation and lesions of the locus coeruleus. Hexobarbital sleeping time was observed in isolated and nonisolated rats with lesioned locus coeruleus (LC). Isolated animals were divided into 2 groups: aggressive (killers) and indifferent (nonkillers). Each group included rats with no lesion, with sham lesion and with LC lesion. Hexobarbital sleeping time was prolonged in nonisolated male, but not female, rats with lesioned LC (7 and 14 days after the lesion). This effect was not observed in animals previously isolated for 3 weeks. These results suggest that the LC plays an important role in the mechanisms of barbiturate sleep, but this effect may be related to the emotionality of animals.


Progesterone: examination of its postulated inhibitory actions on lordosis during the rat estrous cycle.


Medial preoptic and anterior hypothalamic lesions: influences on aggressive behavior in female hamsters.


Placentophagia in nonpregnant rats: influence of estrous cycle stage and birthplace.


Behavioral disturbances in a two-way shuttle-box in congenitally jaundiced Gunn rats.


Poison induced pica in rats.

Poison induced pica in rats.


Effects of genital stimulation upon spinal reflex activity of female cats under various hormonal conditions.


Intruder gonadectomy and elicitation of territorial aggression in the rat.


Effect of neonatal surgery on adult fighting and spacing in mice (Mus musculus).


Intellectual differences in relation to personal and family handedness.


The state of medicinal science.

The state of medicinal science.


Study of pineal regulation mechanism in genital development--influence of light and drugs on genital organs.


A simple method for counting antibody bound labelled steroids. A simple method is described for the counting of tritiated antibody-bound steroid after acidification and extraction into a toluene based scintillant. The resulting count rate is stable and quenching is minimal. The method give improved count rates when compared with methods employing scintillants containing methanol, dioxane, or Triton and compares favourably with methods involving pre-heating of antibody-bound steroid or extraction of free steroids after the addition of ammonium sulphate. A specific antibody for estradiol has been used to illustrate the application of the technique to antibody titration curves and standard curves.


O-(Carboxymethyl)oxime steroidal haptens linked in the C3 position: study of the characteristics of antibodies against 17alpha-hydroxyprogesterone and testosterone and of their evolution with time. The production of highly sensitive and specific antisera against 17alpha-hydroxyprogesterone (17 OHP) is reported. 17 OHP was rendered antigenic by covalent linkage to bovine serum albumin through position 3 of the steroid. An unambiguous method to prepare the mono-3-0-(carboxy-methyl) oxime derivative (CMO) of 17 OHP is described starting from 17 OHP-acetate. Antisera raised in rabbits were of high affinity for 17 OHP (Ka = 1 to 2 x 10(10) L/mole) and showed very little (less than 0.7%) or no cross reaction with a variety of steroids. Cross-reaction with 17alpha-hydroxy pregnenolone was however significant. When studied in relation to time, cross-reaction of the latter steroid decreased significantly (18 to 2%) while Ka remained at the same level. The same study of the evolution with time (up to 600 days) of the characteristics of antisera raised against the 3 CMO derivative of testosterone is also reported.


Parkinsonism and neurogenic bladder. Experimental and clinical observations. In a group of patients suffering from Parkinson's disease, beside neurogenic bladder dysfunction, we have also found dysfunction affecting the external sphincter musculature. Treatment with L-Dopa probably improves the urethral symptoms by providing a relaxing effect on the urethral closure pressur together with better coordination of the pelvic floor and external sphincter Mechanism during micturition. The effect was parallel to the improvement in Parkinsonion symptoms. Experimental studies demonstrate the ability of L-Dopa to reduce urethral closure pressure and this effect was related to a central effect on the skeletal musculature.


Oestrous behaviour in a herd of dairy cows. A group of 60 housed Friesian cows were observed continuously for a period of 25 days, during which time all cows were recorded for incidence of mounting activity and 18 selected cows were recorded for various aspects of maintenance activity. All 60 cows were judged as showing oestrus. Average duration of oestrus (+/-SD) in 33 cows was 14-9 +/- 4-7 hours, and the cows were mounted 56-3 +/- 34-8 times. The greatest mounting activity was associated with the night hours. There was no diurnal pattern of onset of oestrus. The majority of mounting activity (79 per cent) occurred in the cubicle area of the building. Comparison of maintenance activities showed that oestrous cows spent, on average, less time standing in a cubicle (P less than 0-01), lying in a cubicle (P less than 0-001) and more time standing elsewhere (P less than 0-001) than non-oestrous cows. The results are discussed in relation to oestrus detection.


The importance of gonadothropin assays in the clinical follow up patients with germinal tumors of the testis. Clinical-hormone studied were done on 34 patients with germinal tumors of the testis. The gonadotropin titres varied from normal to highly elevated values. Only in 4 cases (11.77%), however, were the gonadotropin titres above 10,000 mouse units/24 hours. These 4 were among the 9 cases (26.47%) with positive pregnancy tests. Gynaecomastia was present in 4 patients (11.77%). Total estrogens were assayed in these 4 cases and were found to be high. Gynaecomastia is attributed to excess estrogens. Elevated gonadotropin titres were found predominantly in cases of embryonal carcinoma, teratocarcinoma and choriocarcinoma, as well as in the most advanced clinical stages. As regards the correlation between gonadotropin titres and course of the tumor, it was found that the higher the titre the worse the prognosis. The results suggest that hormonal assays are of value in the clinical follow-up of testicular germinal tumors and should therefore be carried out in association with other clinical parameters.


Effect of lactation on the immune response to gastrointestinal nematodes. The immune expulsion of gastrointestinal nematodes is impaired during lactation by the inhibition of the lymphocyte mediated component. As a result the population of worms may increase. At the same time, the fecundity of female worms in previously immune hosts may increase to approach that of worms in fully susceptible animals. There is good evidence that these events are primarily endocrinal in origin but although prolactin is probably involved, certain anomalies exist. These may reflect differences in the secretion pattern of the hormone in different phases of reproduction or they may indicate an interrelationship with a second hormone, for instance, adrenal glucocorticoids.


Erysipelothrix insidiosa endocarditis. A report of two cases in Jamaica.


Effect of sodium fluoride on glycolysis in human erythrocytes and Ehrlich ascites tumour cells in vitro. In human erythrocytes and Ehrlich ascites tumour cells, NaF inhibites aerobic glucose utilization and lactate formation. The inhibition of glycolysis was accompanied by a decrease in cellular pyruvate and ATP, and by accumulation of 2-hosphoenolpyruvate. These results and direct enzymatic determinations showed that fluoride inhibits, in addition to enolase (phosphopyruvate hydratase, EC 4.2.1.11), also pyruvate kinase.


Variations in the spontaneous activity of the uterine muscle in vitro and in situ and its response to oxytocin. A study is made of the contractile and bioelectrical activities of the uterine muscle of guinea-pig in vitro and of rabbit in vitro and in situ, as well as their Oxytocin-induced changes upon different balance of the ovarial hormones. In rabbits in situ the uterine muscle contractions are longer and are recorded with a slower rhythm than in vitro. Both in situ and in vitro the sensitivity of the myometrium to Oxytocin is lower upon domination of progesteron and higher upon domination of oestrogen. In guinea pigs the myometrium is least sensitive to Oxytocin in the juvenile animals as compared with the sexually mature ones. The sensitivity of the guinea-pig myometrium to oxytocin in the various phases of the oestral cycle is weakest during dioestrus and strongest during oestrus.


Exocrine pancreatic function measured by secretin-pancreozymin test in chronic duodenal ulcer.


Pharmacological analysis of certain mechanisms of morphine addiction. The effects of L-Dopa, Methysergid, Diphenhydramine hydrochloride and LSD on the development of morphine dependence and the abstience syndrome after its withdrawal, were tested in experiments on 200 male Wistar albino rats. L-Dopa had no efect on the development of physical morphine dependence, while Methysergid prevented its development. Applied in rats during the abstinence syndrome, LSD intensified their aggressivity with no influence on the analgesic effect of morphine. Diphenhydramine reduced the aggressiveness of the rats during the abstinence syndrome. Biochemical tests show that in morphine-tolerant rats there was an increase in the content of brain serotonin, less of dopamine and no changes in noradrenaline. The significance of the brain levels of serotonin, dopamine and noradrenaline for the development of physical morphine-dependence is discussed. It is pointed out that serotonin and dopamine play an important role both for the origin of the physical morphine dependence, and in the abstinence syndrome after its withdrawal.


The induction of cytochrome P-450 by hypoxia.


Control mechanisms of oxygen and glucose utilization in tumours.


Experimental and theoretical analysis of oxygen transport in fetal brain. Based on the results obtained in this study and the results of others it seems safe to conclude the following: 1) Fetal brain PO2 values are considerably lower than those found in adult brain. 2) Administration of 100% oxygen to the mother can (but not always) significantly raise the PO2 at a specific point in the fetal cortex. 3) The response of fetal brain PO2 to changes in maternal arterial PO2 is delayed by a finite quantity of time of the order of magnitude of 38 seconds. 4) The time required for the fetal brain PO2 to reach a minimum following a decrease in the PO2 of maternal arterial blood coincides closely with the time required for the maternal arterial PO2 to reach its minimum plus the pure transport delay time (38 seconds). 5) The fetus has available a control mechanism which acts to compensate for periods of reduced PO2 in the microenvironment of the fetal cortex.


Development and adaptation of heart mitochondrial respiratory chain function in fetus and in newborn.


An electron microscopic study of the lens epithelium in a mouse strain with hereditary cataract.


Nephrotic syndrome with early renal amyloidosis in juvenile rheumatoid arthritis.


Compositional data on some Persian bezoars. Fourteen Bezoars from Persia, used in past times and even to-day as a medicine or as a health-preserving precious tone, are examined. Among the concretions ellagic acid prevails. Some are bile pigmented or calcite stones. Other bezoars are mineral substances or artifacts.


The rapid onset of inhibition of antibody-forming cell proliferation upon an increase in density of cellular suspensions cultured in vitro. It was shown previously that the development of primary immune response in vitro in the Mishell-Dutton system was strongly inhibited by increased cell densities (Gurvich et al., Immunology 1975. 28: 271). In the present work, the rate of onset of this inhibition was studied in C57BL/6 mouse spleen cell suspensions during the phase of exponential increase of antibody-forming cells (AFC) after 3 days' cultivation in vitro with the antigen. It has been shown that the increase in AFC number is very soon inhibited following an increase in the cellular density, the inhibition already being evident within 2 or 4 h. Parallel reduction in incorporation of radioactive precursors in DNA and especially RNA is observed, whereas inhibition of protein synthesis was delayed.


Retinal detachment secondary to branch vein occlusion: Part I. Eight patients with retinal detachment secondary to branch vein occlusion were studied. Retinal detachment secondary to branch vein occlusion occurs when the vein occlusion is severe and there is marked capillary nonperfusion and leakage. The detachment is limited to the area of the occluded vein and does not extend beyond the equator. Usually the detachment is shallow; however, it can be bullous as demonstrated in 3 of our patients. Fluorescein angiography revealed the typical findings associated with branch vein occlusion, in addition to late pooling of the dye into the fluid in the subretinal space. In each of the 6 cases treated by laser photocoagulation, reattachment of the retina occurred. The disease is discussed from the standpoint of ocular findings, fluorescein angiography, diagnosis and differential diagnosis, course, treatment, and prognosis.


Retinal detachment secondary to branch vein occlusion: Part II.


The possibility of a flaw underlying Weinberg's differential rule. There seems rather good evidence that there is a flaw underlying Weinberg's Differential Rule, and that among DZ twin pairs, there are perhaps eight same-sexed pairs to every seven opposite-sexed pairs.


Paternal age, stillbirths and mutation.

Paternal age, stillbirths and mutation. Previous suggestions that accumulation of mutations in the germ line of ageing fathers causes an increased stillbirth rate were based on analyses of data which were heterogeneous for social variables whose effects were confounded with possible paternal age effects. This study was confined to the analysis of stillbirth rates of groups of women selected to be homogeneous for education, previous pregnancy outcomes, age, race and marital status. It is concluded that stillbirth rates do not increase with father's age independently of maternal variables. Neither accumulation of mutations in the paternal germ line nor other biological change associated with father's age can be inferred to cause an increase in risk of stillbirth with increasing paternal age.


The effect of halides on the equilibrium and reactivity of aspartate aminotransferase.


Reaction of antibody to normal human hypoxanthine phosphoribosyltransferase with products of mutant genes.


Variety of 2,4-D metabolic pathways in plants; its significance in developing analytical methods for herbicides residues. 2,4-D in plants very rapidly undergoes various transformations and its predominant metabolic pathways and rates vary with different plant species. In bean and soybean plants major 2,4-D metabolites are 4-O-beta-D-glucosides of 4-hydroxy-2,5-dichloro- and 4-hydroxy-2,3-dichloro-phenoxy-acetic acids; in addition, considerable amounts of N-(2,4-dichlorophenoxyacetyl)-L-aspartic and N-(2,4-dichlorophenoxyacetyl)-L-glutamic acids are accumulating in them. Among 2,4-D metabolites in cereals there prevailed 1-O-(2,4-dichlorophenoxyacetyl)-beta-D-glucose while the glycoside of 2,4-dichlorophenol prevailed in strawberry plants.


[Clinical studies on results of repair of ventricular septal defect associated with severe pulmonary hypertension. Mortality and hemodynamic changes in various age groups].


A note on the kinetics of uptake of D-glucose by the food yeast, Candida utilis. Unlike other yeasts so far investigated, the D-glucose carrier of Candida utilis (strain NCYC 737) appears to change affinity for D-glucose according to its exogenous concentration. When the concentration of D-glucose was less than 0.4 mM, the apparent Km approximately 0.2 mM; at greater than 0.4 mM, the Km approximately 10 mM.


Synthesis and biological properties of derivatives of 3-methyl-5-aminoisothiazolo-4-carboxylic acid. The reaction of 3-methyl-5-aminoisothiazolo-4-carboxylic acid with the chlorides of chloroacetaic acid and chloropropionic acid gave 3-methyl-5-chloroacetyl- and 5-chloropropionylisothiazolo-4-carboxylic acids, which upon heating in anhydrous ethanol with aliphatic and aromatic amines gave the respective 5-aminoacetyl and amino-propionyl derivatives of these acids. Iodoacetyloaminoisothiazolo-4-carboxylic acid in reaction with ammonia was converted in 3-methylo-5-aminoacetylo-aminoisothiazolo-4-carboxylic acid, which upon heating in toluene with isocyanates and isothiocyanates gave the respective derivatives of urea and thiourea. Some of the synthesized compounds showed psychotropic and cytostatic activity.


UV irradiation of interferon-treated chick embryo cells enhances Sindbis virus growth.


Growth, purification and characterization of Semliki Forest virus in Ehrlich ascites tumor cell suspensions. The growth of Semliki Forest Virus (SFV) in suspension cultures of Ehrlich Ascites (EA) cells and its purification is described. Large volumes of virus material were concentrated by filtration with DIAFLO XM-300 membrane and precipitation with ammonium sulfate. A combination of protamine sulfate treatment, centrifugation of the virus onto a 50 per cent sucrose cushion, and sedimentation through a 5--30 per cent sucrose density gradient was employed. The purified virus particles were homogeneous as revealed by electron microscopy, by moving boundary electrophoresis, and by polyacrylamide gel electrophoresis. Virus suspensions containing 1 mg/ml of protein had a hemagglutinin titer of 1:12,000 when measured with 0.25 per cent goose red blood cells.


The role of the Tasmanian devil in the epizootiology of ovine cysticercosis and echinococcosis. Tasmanian devils were fed infective cystic material of Taenia ovis, T. hydatigena and Echinococcus granulosus and later killed and examined for adult tapeworms. No infections with T. ovis were found after feeding 23 cysts to 8 devils. T. hydatigena were recovered from 5 to 41 devils and 10 worms established after feeding 417 cysticerci. No E. granulosus were recovered from any of 3 devils. Specimens of T. hydatigena appeared to develop as well in devils as in dogs. From these and previous results devils could be successful hosts to T. hydatigena and T. ovis. A survey of 320 devils failed to detect any natural infections with any of these 3 species.


Lymnaea columella in aquariums.

Lymnaea columella in aquariums.


Electroconvulsive shock- or puromycin-induced retention deficits in goldfish given two active-avoidance sessions.


Modulation of passive-avoidance behavior of rats by intracerebroventricular administration of antivasopressin serum.


Exposure to the odor of food determines the eating preferences of rat pups.


Prenatal influences on the responsivity of neonate rats.


Retrieval facilitation in normal and amnesic rats with kinesthetic feedback.


Variable temporal gradients of retrograde amnesia: contingency on tasks and species.


Comparisons of sexual receptivity and proceptivity in female hamsters.


Progesterone and 5alpha-reduced metabolites: facilitation of lordosis behavior and brain uptake in female hamsters.


Pattern of food intake and body weight gain in aged, noncycling female rats.


Studies on the behaviour of cyprinodont fish. III. The temporal patterning of aggression in Aphyosemion striatum (Boulenger).


Effects of male aggressiveness on behavioural transitions in the reproductive cycle of the Barbary dove.


Purification and some properties of a medium-chain acyl-thioester hydrolase from lactating-rabbit mammary gland which terminates chain elongation in fatty acid synthesis. 1. An acyl-thioester hydrolase was isolated from the cytosol of lactating-rabbit mammary gland. The purified enzyme terminates fatty acid synthesis at medium-chain (C8:0-C12:0) acids when it is incubated with fatty acid synthetase and rate-limiting concentrations of malonyl-CoA. These acids are characteristic products of the lactating gland. 2. The mol.wt. of the enzyme is 29000+/-500 (mean+/-S.D. of three independent preparations), as estimated by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 3. The enzyme also hydrolyses acyl-CoA esters of chain lengths C10:0-C16:0 when these are used as model substrates. The greatest activity was towards dodecanoyl-CoA, and the three preparations had specific activities of 305, 1130 and 2010 nmol of dodecanoyl-CoA hydrolysed/min per mg of protein when 56muM substrate was used. 4. The way in which this enzyme controls the synthesis of medium-chain fatty acids by fatty acid synthetase is briefly discussed.


Administration of peripheral-blood rat-lymphocytes stimulated "in vitro" with human lymphokines and spleen colonies in the total body irradiated rat. It was previously reported that PHA-incubation of a pool of peripheral-blood lymphocytes before their i.v. injection into rats submitted to total body irradiation, stimulates spleen colony formation and growth. On the same model, the present study has investigated the effect of lymphocyte preincubation with supernates obtained in short term cultures from human lymphocytes prestimulated with PHA (lymphokines). The "in vitro" culture of rat lymphocytes in a medium supplemented with human lymphokines showed either a marked increase of lymphocyte survival rate, or significant stimulation of lymphocyte blastogenesis, but at an extent much lower than that caused by PHA, also because in this particular experiment the culture medium was supplemented with too little amount of lymphokines. These data support the interpretation that human lymphokines may act across the species barriers. Peripheral-blood rat lymphocytes prestimulated with human lymphokines, and then injected i.v. into rats previously submitted to total body irradiation, caused significant increase in the spleen weight, as well as formation of spleen colonies quite larger and with higher erythroid differentiation - though less numerous than in the controls (i.e., in the rats injected just with untreated lymphocytes). This behaviour may be due to the tendency to merge together of two or more colonies in a single giant colony, and supports the interpretation that immune-competent lymphocytes activated either with PHA or with lymphokines may stimulate spleen colony growth and erythroid differentiation, though at different extents.


The effect of narcotic and narcotic-antagonist drugs in the newborn rabbit. The newborn rabbit responds to acute anoxia, as a result of breathing nitrogen, with successive periods of dyspnoea, primary apnoea, gasping and terminal apnoea. Pethidine caused an increase in the period of primary apnoea and a decrease in the duration and rate of gasping. When nalorphine was combined with pethidine the period of primary apnoea was still increased although the duration and number of gasps were restored to control values. Naloxone, in contrast, acted as a mild respiratory stimulant, shown as a longer phase of dyspnoea. Also it completely abolished the respiratory depression produced by pethidine. Naloxone may be preferable to nalorphine as a drug to reverse the effects of pethidine immediately after birth.


Effect of halothane and diethyl ether on the circulatory response to carbon dioxide in the isolated perfused cat lung. Constant flow perfusion of the pulmonary circulation was established in isolated cat lungs. These were ventilated with 5% carbon dioxide in oxygen in order to maintain a near-normal carbon dioxide tension and acid-base status in the perfusing blood. The alteration of pulmonary vascular resistance in response to a change in inspired carbon dioxide concentration from 5% to 10% was investigated before, during and after the administration of 1% halothane (in 16 perfusions) or 5% diethyl ether (in 8 perfusions). An increase of inspired carbon dioxide concentration caused a significant increase in pulmonary vascular resistance, but the magnitude of the increase was diminished during the administration of both anaesthetic agents. The response increased again after the anaesthetics were withdrawn. The administration of halothane during ventilation with 5% carbon dioxide caused a significant reduction of pulmonary vascular resistance whilst diethyl ether resulted in a significant increase in this measurement. It is suggested that inhalation anaesthetic agents may increase ventilation/perfusion mismatching by altering the normal vasoconstrictor response to increased alveolar PCO2;


Kinetics of inhibition of acetylcholinesterase by spin labeled acetylcholine analogs. A series of spin labeled acetycholine analogs, in which the number of methylene groups between the quaternary nitrogen and the alcohol oxygen ranged between 1-5, have been examined as inhibitors of electric eel acetylcholinesterase. Evidence is presented suggesting that inhibition of acetylocholinesterase by the spin labeled ACH analogs is due to the high affinity of these compounds for the enzyme, inhibition is competitive and reversible. It has been shown that complex formation is of major importance in the reaction between spin labeled ACH analogs and acetylcholinesterase. The acetylation step has been shown to occur by demonstrating that the leaving group is released as the reaction proceeds. Complex formation has been demonstrated by means of kinetic criteria. Kinetic parameter have been measured for the five compounds, and correlations with alkaline hydrolysis are disussed.


Division of the external urethral sphincter in the neuropathic bladder: a twenty years' review. It is now twenty years since the authors first performed division of the external sphincter region in the treatment of the neuropathic bladder. Although a ten year report was published in 1967, it was decided to review all the patients at the end of the twenty year period. The rationale of the operation in the upper motor neurone lesion has been confirmed by modern investigative techniques, while it appears from recent work that the success of the procedure in the lower motor neurone case is due to division of plain muscle which is subjected to excessive sympathetic stimulation. It is the authors' firm conviction that long term catheterization, whether permanent or intermittent is a confession of failure and can be avoided in the vast majority of patients. The operation has proved of permanent benefit especially with the regard to the elimination of residual urine. Further, hydronephrosis, and renal infection and failure, are also benefited in many cases. These factors are of great importance in a condition in which late morbidity and mortality has been usually due to renal causes.


Selective ploidy of chromosomes in ascites tumor cells.


Amino acids content in the proteins of fresh- and salt-water crustaceans.


Anterior detrusor tube repair for urinary incontinence in children. The technique, complications and results of an anterior detrusor tube repair for urinary incontinence in children is described. It appears that this procedure is appropriate only for selected cases of urinary incontinence but that it is an operation which should be within the paediatric urologist's repertoire. It is simple to perform, but care should be taken, by omental packing, to prevent a sharp posterior lip to the newly formed bladder neck.


Natural occurrence of an inhibitor of mammalian cell growth in human and mouse cells of normal and tumor origin. N6-(delta2-isopentenyl)adenosine was found both as a component of tRNA and as the cytoplasmic mononucleotide in human leukemic lymphoblasts and myeloblasts from peripheral blood and bone marrow samples. This hypermodified nucleotide was also found in the tRNA and as a mononucleotide in human (MRC-5 and KB) and mouse (A9, FLV, LM, and RAG) cell lines. The relative amounts of this hypermodified nucleotide in the tRNA of the cell lines and the human leukemias were similar (the mean value being 0.06 +/- 0.03 mole % of the total tRNA nucleotide content); whereas the amounts occurring as the free cytoplasmic mononucleotide were more varied but still comparable (the mean value being 0.53 +/- .09 mole % of all cytoplasmic nucleotides) for all cells investigated with the notable exception of all normal, diploid cell lines under study (0.04 mole%). A possible relationship of the free cytoplasmic mononucleotide with the nucleotide in the tRNA for control of mammalian cell protein synthesis in vivo was investigated by addition of N6-(delta2-isopentenyl)adenosine to the culture medium. The exogenously added nucleoside caused inhibition of cell growth within 3 h and cell death within 36 h at concentrations as low as 0.4 muM. No comparable effects were seen when adenosine, adenine, or N6-(delta2-isopentenyl)-adenine were added to the cultures. The simultaneous presence of adenosine in cultures containing N6-(delta2-isopentenyl)adenosine did not alter the detrimental effects of the hypermodified nucleoside on cell growth even when the concentration of adenosine was 50-fold that of N6-(delta2-isopentenyl)adenosine. Addition of N6-(delta2-isopentenyl)adenosine to cell cultures caused within the first 6 h a significant reduction in the rates of RNA and protein synthesis; whereas DNA synthesis continued at a rate comparable to control and adenosine-treated cells for 18 h before decreasing.


Hydrocortisone inhibits the spontaneous detachment of viable mammary tumor cells from monolayer cultures. Primary mammary adenocarcinomas of C3H mice were dissociated to single cells. These cells were seeded at a density of 5 x 10(5)/cm2 substrate area and were grown as monolayers for 36 days in high-serum medium supplemented with insulin. Cultures became confluent within a few days and confluence was maintained throughout the culture period. Viable cells (representing amitotic cell population) were released spontaneously from the confluent monolayer and could be harvested from the culture fluid. The rate of cell release declined after about 30 days, apparently due to mitotic pool depletion. Release of cells from the monolayer was strongly depressed in medium containing hydrocortisone. The cell release event and its alteration by hydrocortisone can be interpreted as reflecting the propensity towards shedding of cells from these tumors in vivo and the alteration of metastatic incidence by adrenal steroids.


Presence of cellular rentinol and retinoic acid binding proteins in experimental rumors. Cellular retinol and retinoic acid binding proteins were detected in mouse skin papillomas, human adenocarcinoma HAD-1, Dunning Leukemia, Walker 256 carcinosarcoma and mammary adenocarcinoma MAC-1. A chondrosarcoma and Sarcoma 180 apparently contain only the cellular retinoic acid binding protein. Neither protein could be detected in Ehrlich carcinoma and L1210 leukemia. The presence of these proteins might be necessary for sensitivity to retinoid therapy.


Excision of epithelial tumors: CO2 laser versus conventional methods. In a comparative experimental study, excisions of a transplanted Lewis lung carcinoma in BDF1 mice were performed by means of the CO2 laser and conventional methods, namely common scalpel and diathermy. The results showed a significant reduction in tumor recurrence and animal mortality rates (27.5% vs. 75% and 45%) after tumor excision with the laser in the early stage (5th day) of tumor development. This finding, in addition to the surgical properties of the CO2 laser, suggests that early excision using this modality is a rational treatment of this type of tumor.


Common metabolites of N-nitroso-2,6-dimethylomorpholine and N-nitroso-bis(2-oxopropyl)amine in the Syrian hamster. N-Nitroso-2,6-demethylmorpholine (NDMM) administered intraperitoneally to Syrian hamsters was metabolized  to N-nitroso-bis(2-hydroxypropy)(2-oxopropyl)amine(HPOP) and N-nitroso-bis(2-hydroxpropyl)amine (BHP) which were identified in blood and urine. The potent pancreatic carcinogen N-nitroso-bis(2-oxoproply)amine was previously shown to form the same metabolites. Preliminary results indicate that NDMM also induces pancreatic and other tumors in Syrian hamsters, similar to those found following BHP treatment.


Phase I alternate-day dose study of chromomycin A3. Chromomycin A3 was given to 43 patients with metastatic cancer in order to determine the tolerable dose when the drug was administered on an every-other-day dose schedule for a total of five iv push injections, with the course of therapy being repeated every 4 weeks. At least three patients were entered at each dose level, graduated in 0.1-mg/m2 increments between 0.7 and 1.6 mg/m2. The most common (19 patients) side effect was nausea and/or vomiting, but this was usually mild, lasted for a few hours, and diminished in severity with repeated injections. Skin necrosis due to drug extravasation was a problem early in the study, but was eliminated by injecting the drug through iv tubing. Transient elevations in SGOT and alkaline phosphatase levels were observed, but proved not to be of serious consequence. Renal toxicity proved to be the limiting factor in therapy. However, a dose level of 1.3 mg/m2 was found to be a tolerable level of drug administration in previously untreated patients. Objective tumor responses were noted in four patients (Hodgkin's disease, embryonal rhabdomyosarcoma, adenocarcinoma of the lung, and malignant melanoma).


Structural studies on the extracellular polysaccharide of the red alga, Porhyridium. Partial acid hydrolyzates of the extracellular polysaccharide from Porphyridium cruentum yield three disaccharides and two uronic acids. These constitute all of the uronic acid in the polymer. The novel disaccharides are 3-O(alpha-D-glucopyranosyluronic acid)-L-galactose, 3-O-(2-O-methyl-alpha-D-glucopyranosyluronic acid)-D-galactose, and 3-O-(2-O-methly-alpha-D-glucopyranosyluronic acid)-D-glucose. The polyanion of high molecular weight contains D- and L-galactose, xylose, D-glucose, D-glucuronic acid and 2-O-methyl-D-glucuronic acid, and sulfate in molar ratio (relative to D-glucose) of 2.12:2.42:1.00:1.22:2.61. Preliminary periodate-oxidation studies suggest that the hexose and uronic acids are joined to other residues by (1 leads to 3) glycosidic linkages. About one-half of the xylose residues are (1 leads to 3)-linked.


Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. I. Cell kinetic and biologic effects in cultured L1210, human epidermoid No. 2, and adenocarcinoma 755 cells. Experimental results obtained with cultured L1210, human epidermoid No. 2, and Adenocarcinoma 755 cells are consistent in showing that inhibition of proliferation of the cells by 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride is accompanied by cell enlargement. Although cells initially in the G2 phase when exposure to the agent is begun can probably proceed through mitosis and divide, cells that are initially in G1 and S phases accumulate in the G2 phase. Progression of cells to G2 phase during the period of exposure to the agent is not a requisite for cell-killing, because cells exposed for periods insufficient to permit their accumulation in G2 are killed.


Microinjection studies of duck globin messenger RNA translation in human and avian cells. Microinjection techniques were used for the study of the translation of heterospecific messenger RNAs in living cells. Duck globin messenger RNAs, in the form of polysomes, messenger ribonucleoprotein particles, or free mRNAs, were injected into cells of human origin (HeLa), and the subsequent appearance and accumulation of avian globin were measured by specific immunofluorescence techniques. Globin accumulated within a high proportion of HeLa cells for at least 25 hr following injection, indicating the intracellular stability of the heterospecific globin messenger RNA and the fact that mRNA initially associated with more complex structures could be translated in the HeLa cytoplasm. In similar experiments, duck reticulocyte polysomes were shown to be translated in duck embryo cells but not in embryonic chick liver cells. The latter, however, could be shown to withstand the microinjection procedure as judged by their capacity to respond normally to inducers and inhibitors of the synthesis of alpha-aminolevulinic acid synthetase. HeLa cells injected with duck hemoglobin divide at normal or nearly normal rates following the injection, but their globin content diminishes, in contrast with the increasing globin content of cells receiving duck reticulocyte polysomes, mRNP particles, or free mRNA.