[Lupine, a contribution to the human food supply. 3. Nutritional physiological study with lupine (Lupinus albus) flour]. Lupinus albus flour doses of 58.9 +/- 9.6 g have been given to 20 persons. This sweet lupine flour has been digestible without complications in all cases. There have been no significant changes of hemoglobine, hematocrite, total protein, urea, bilirubine, and SGOT in the blood. So the lupine may be used for improvement of protein supply in men under the criteria that (1) the alkaloid content of the seed does not exceed 0.02%, (2) the seed itself contains no secondary fungi which may cause a lupinosis.


[Some clinical and paraclinical observations about the syndrome of "acropathie ulcero-mutilante" (author's transl)]. A case of "acropathie ulcero-mutilante" is reported, some features of which contribute to a better knowledge of the following controversial points: a) the occurrence of sporadic non familiar cases; b) the existence of degenerative changes in the motor pathways; c) the hystochemical picture, which has been not previously described. This case confirm sporadicity and degenerative changes in motor pathways. The histochemical picture show typical signs of denervation.


[Epidemiological study on coronary risk factors in a population of clerks in Parma. Methods of research and 1st results]. After a review of current literature, the AA. present the purposes and the methods of an epidemiological study on coronary risk factors in selected bank-clerks of Parma, in view to correlate the dietary factors, possible methabolic alterations, psychical behaviour, social and environmental position and coronary risk evaluated by electrocardiographic stress test. In this respect, the AA. report and discuss, as example of the reliability and validity of the investigative model followed, the preliminary results observed in the 274 subjects up to this time controlled.


[Cystine-amino-peptidase (C.A.P.) and D.B.P. in "at risk" pregnancy with "poor intrauterine fetale growth" (P.I.F.G.) (author's transl)]. The normal range of serum cystine-amino-peptidase (C.A.P.) in 54 cases of uncomplicated pregnancies was established. 21 patients whose pregnancies were though to be "at risk" were serially monitored by sonar biparietal cephalometry and serum cystine-amino-peptidase determination. The results show that exists a correlation between C.A.P. and biparietal cephalometry values. Furthermore the "predictive power" towards neonatal conditions (by birth weight and Apgar score determination) was of 77,55% for the biparietal cephalometry and 76,10% for C.A.P.


Antibodies to spermatozoa. VII humoral and cellular aspects of sperm inmunity and infertility. The occurrence of sperm antibody in serum and cervical mucus of women from intertile couples in the serum of their male partners, as well as cellular immunity to sperm, has been studied by agglutination and immobilization techniques. For a total of about 260 couples, the tests on serum showed that 18% of the women and 8% of the men were positive by the Kibrick technique and that 15% of the women and 4% of the men were positive by the F-D technique. The women who were positive in their cervical mucus were 8% of the group by the K-agg (Kibrick agglutination) technique, 2% by the MIS-agg. (Microscale agglutination) technique, and 40% by the MIS-imm. (Microscale immobilization) tecnique. In considering all three techniques. 42% of a group of 132 women were positive. Cellular immunity to sperm, by the Migration Inhibition method, was positive in 18% and zero per cent of infertile and fertile women, respectively.


"Ischemic" heart disease in fire fighters with normal coronary arteries. Near maximal stress testing conducted on a group (N = 90) of randomly selected Los Angeles City fire fighters (age 40-59 yrs.) revealed that 10% had ischemic ECG changes. These ischemic ECG responses were confirmed during a second test conducted two to four weeks after the initial test. Coronary heart disease (CHD) risk factor analysis revealed that in general the men were not at high risk for CHD. Six of the nine men elected to undergo cardiac catheterization and angiography. One patient had severe triple vessel disease and subsequently underwent aorto-coronary bypass surgery. Another had 50% obstruction in the circumflex branch of the left coronary while the other four men had no visable signs of coronary obstruction. The men with "normal" coronaries, however, did show signs of abnormal cardiac function during atrial pacing. One man had cardiac enlargement, hypokinesis, ischemic ECG and abnormal lactate metabolism. Another had abnormal lactate metabolism and ischemic ECG. A third man had moderate cardiac enlargement with anterior wall hypokinesis. The fourth had ischemic ECG changes with angina but otherwise normal cardiac function. All four of these men had pressures which were within normal limits. These data show that some fire fighters have "ischemic" heart disease with patent coronary arteries. This disease may be due to job related factors (i.e. carbon monoxide and other noxious fumes, catecholamines, etc.) which reduce myocardial oxygen supply or greatly increase myocardial oxygen demands.


Treatment of painful neuromas of sensory nerves in the hand: a comparison of traditional and newer methods. The results of treatment of 348 painful neuromas of sensory nerves of the hand in 172 patients were evaluated. Three hundred and sixteen were treated by simple excisional neurectomy and these results may be used for comparison with other methods. Sixty-five percent had an excellent or satisfactory result from a single such procedure. A repeated neurectomy improved the results to 78 percent. The use of silicone rubber caps as a secondary procedure over the nerve stump in 32 cases did not improve the results. A technique of funicular resection with epineurial ligation in 45 patients with neuromas achieved about the same percentage of good results as did simple excisional neurectomy. The ideal treatment is not at hand yet, but at the present time it is recommended that treatment should consist of excisional neurectomy, repeated at least one if necessary.


Reconstructive hand surgery in tetraplegia, stroke, and cerebral palsy: some basic concepts in physiology and neurology. The examination of hands in tetraplegia, stroke, and cerebral palsy must include evaluation of the state of the ligaments the muscles available for motors for tendon transfer, and, most important, the areas of sensibility. The test for two point discrimination is the most valuable in providing information regarding both exteroception and proprioception. Done properly, this test provides more useful information than any other used currently.


Effect of stress on serotonin concentration and tryptophan hydroxylase activity of brain nuclei. The effects of a single stressful stimulus on serotonin (5-HT) concentration and of repeated stressful stimuli on tryptophan hydroxylase (THy) activity were measured in individual hypothalamic nuclei and other rat brain regions using specific sensitive radioisotopic enzymatic microassays. Two h after formalin injection, 5-HT levels were increased in the dorsal raphe (RDN). Acute immobilization stress, however, reduced the concentrations of 5-HT in several of the hypothalamic nuclei: the medium eminence (ME), lateral amygdaloid nucleus, hippocampus, cingulate cortex (CCX) and RDN. Five consecutive daily immobilization periods failed to alter THy activity in any region examined. These results suggest a rapid release of 5-HT both from the cells and the axon terminals in the central nervous system, and failure, even with repeated stresses, to elicit induction of increased levels of the biosynthetic enzyme regulating the synthesis of the neurotransmitter.


Pollution-reduced Kjeldahl method for crude protein. Pollution from the Kjeldahl method for crude protein has been reduced by substituting a low level of copper (0.04 g CuSO4) for the mercury (0.7 g HgO) specified in the AOAC official method, 2.049. Adjustments were made in the salt-acid ratio so the new system could handle hard-to-digest samples in a reasonable time. The new method was rugged for lysine. HCl. It is designed to be used for crude protein in feeds or similar Kjeldahl work. Precision and accuracy were equal to or better than that for the official method in a study of 17 samples analyzed in duplicate on 3 different days. The following samples were used in the study: lysine. HCl, tryptophan, NBS standards, urea, meals, mixed feeds, grains, and forage. The average per cent nitrogen found was 9.52 by the official method and 9.53 by the copper method. The average standard deviation was 0.038 by the official method and 0.033 by the copper method, giving the corresponding relative standard deviations of 0.40 and 0.35%.


Reflection-impulsivity and need for achievement in emotionally disturbed children. Reflection-impulsivity is the cognitive dimension proposed by Kagan and his colleagues to describe the differences in children's resolution to response uncertainty. Impulsive children tend to respond quickly without considering all of the available alternatives and consequently make many mistakes. Reflecttive children consider all of the available alternatives, withhold responding until they have a high probability of being correct, and consequently make few mistakes. The primary dynamic underlying a reflective cognitive style is hypothesized to be a fear of making a mistake: the greater the fear, the more reflective the child is and the more cautiously he performs. On the other hand, minimal anxiety over a potentially inaccurate answer is likely to result in an impulsive performance.


Anti-hypertensive action, time of onset and effects on carbohydrate metabolism of labetalol. 1 Seventeen men, aged 45-57 yr, with essential hypertension showed obvious and, in the standing position, dose-related reductions in blood pressure during treatment with oral labetalol with weekly dose increments. 2 Pulse rate changes were not related to dose but reduced compared with pre-treatment values. 3 No postural hypotension was recorded indicating lack of a dominant alpha-adrenoreceptor-blocking component. 4 There was a small increase in mean fasting blood glucose levels during labetalol treatment but no alteration in insulin activity or response to an oral glucose tolerance test.


Isolation and translation of calvaria procollagen messenger ribonucleic acids. Procollagen messenger ribonucleic acid (mRNA) was isolated from the calvaria of 15-day-old chick embryos by chromatographing total RNA over oligo(dT)-cellulose two times, and then fractionating the twice-bound RNA on 85% Me2SO/0-20% sucrose gradients. When analyzed on 99% formamide gels, the 27-30S fraction had three sharp fluorescent bands, one corresponding to 27S ribosomal RNA (rRNA), the others having mobilities lower than 27S corresponding to molecular weights of 1 700 000 and 1 800 000. In wheat-germ, cell-free extracts, the 27-30S fraction directed the synthesis of two prominent collagenase sensitive polypeptides with mobilities corresponding to the calvaria pro-alpha chain markers. Twelve percent of this [3H]proline-labeled, wheat-germ product could be hydroxylated with prolyl hydroxylase.


Fluorescence energy-transfer measurements between the calcium binding site and the specificity pocket of bovine trypsin using lanthanide probes. Using fluorescence energy-transfer experiments we have measured the distance between the specificity pocket and the calcium ion binding site of bovine pancreatic trypsin. Proflavin and thionine were used to block the specificity site, whereas various lanthanide ions were substituted for the calcium. It was then possible to choose various donor-acceptor pairs which exhibit suitable energy transfer. We have calculated the distance between proflavin and Nd(III), Pr(III), and Ho(III) to be 10.9, and 10.3, and 10.3 A, respectively. This agrees very well with the value of approximately 10 A we obtained between the methyl protons of p-toluamidine (a competitive inhibitor) and Gd(III) using nuclear magnetic resonance techniques (Abbott, F., Gomez, J.E., Birnbaum, E.R., and Darnall, D.W. (1975), Biochemistry 14, 4935). This is strong evidence that, in solution, the calcium binding site is composed of the side chains of Ser-190 and Asp-194.


Incorporation of macromolecules in microparticles: preparation and characteristics. Macromolecules can easily be incorporated in microparticles of polyacrylamide by copolymerization with acrylamide in a water-in-oil emulsion. The microparticles preferably arount 1-3 mum in diameter, will have a macroporous structure formed by the polymeric network. The amount of incorporation of the macromolecules will depend on the structure of the network, which, in turn, will depend on the total amount of monomer (T) and the relative amount of cross-linking agent (C) in the monomeric solution. Two mechanisms are responsible for the incorporation; all macromolecules are, independently of the size, fixed in the threads of polyacrylamide and large ones are entrapped within the network formed by the threads. The amount entrapped will depend on the size of the macromolecule and the mean pore radius of the gel. In microparticles with a total concentration of monomers of 8% and a cross-linking of 25% (T-C=8-25) the biological properties of incorporated macromolecules are retained, due to the macroporous structure, as found in binding studies with albumin. The density of the particles will also depend on C and T and, to some extent, on the protein concentration. Due to the fixation in the polyacrylamide threads, some of the incorporated macromolecules will be exposed on the surface, allowing them to react with, for instance, cells, which cannot penetrate the particles. The optimal conditions for the incorporation of macromolecules in the microparticles are investigated.


[Effect on glucose on levansucrase synthesis by Gluconobacter oxydans]. The effect of glucose on synthesis of levansucrase was studied with Gluconobacter oxydans L-1. Glucose added to the nutritional medium containing sucrose was found to supress its degradation by G. oxydans L-1. At the same time, the lag phase became shorter. Synthesis of levansucrase was inhibited in the nutritional medium containing glucose while the enzymatic activity increased proportionally to the amount of bacterial biomass in the medium containing sorbitol. Addition of glucose to the nutritional medium containing sorbitol prior to inoculation results in a decrease of the differential rate of levansucrase synthesis. The repressory effect of glucose on the enzyme synthesis manifested itself most distinctly at its addition to the culture in the period of bacterial multiplication with the maximum rate.


Separable binding proteins for retinoic acid and retinol in bovine retina. Binding proteins for retinoic acid and retinol were separated from a supernatant prepared from bovine retina. Fraction IV from DEAE-cellulose chromatography bound exogenous [3H] retinoic acid which could not be effectively displaced by retinol, retinal, retinyl acetate or palmitate, but which was readily displaced with excess retinoic acid. [3H] Retinol was bound by fraction V from DEAE-cellulose chromatography and was not displaced by retinal, retinoic acid, retinyl acetate or retinyl palmitate, but was readily displaced by excess retinol. Unlike bovine serum retinol-binding protein, neither intracellular binding protein formed a complex with purified human serum prealbumin. The supernatant from bovine retinas was estimated to contain five times more retinoic acid binding than retinol binder.


A labile acid phosphatase isozyme associated with the surface of vegetative Dictyostelium discoideum cells. A minor acid phosphatase isozyme (acid phosphatase I) of vegetative Dictyostelium discoideum amebae has been shown to be associated exclusively with the external surface of the plasma membrane. The isozyme is not present in phagocytic vacuoles isolated with latex beads. The isozyme disappears from cells removed from nutrient medium and does not reappear during differentiation. When inhibitors of protein synthesis (e.g. cycloheximide, chloral hydrate, concanavalin A) are added to cells growing in nutrient medium, acid phosphatase I is rapidly lost. It appears that the level of protein synthesis need only be moderately reduced (less than 25%) to induce loss of enzyme activity. Treatment with inhibitors of DNA and RNA synthesis for up to 2 h had no effect on isozyme activity. It is postulated that the cells are able to "sense" (through the reduction in levels of protein synthesis) when external conditions become unfavorable, and immediately respond by reducing the activity of enzymes involved in maintaining contact with the extracellular environment. The closed system thought necessary for differentiation would then be created.


Structural characterization of a glycoprotein cellulase, 1,4-beta-D-glucan cellobiohydrolase C from Trichoderma viride. A glycoprotein enzyme, 1,4-beta-D-glucan cellobiohycrolase (EC 3.2.1.91) form C, was purified to electrophoretic homogeneity by a procedure which permitted isolation of gram quantities from a commercial Trichoderma viride culture filtrate preparation. Purified cellobiohydrolase C has an E1%/280 nm = 14.2 and degrades both microcrystalline and phosphoric acid-swollen cellulose to cellobiose. The cellobiohydrolase C contains 26.4, 4.8, 2.4 and 3.4 mol of mannose, glucose, galactose and glucosamine, respectively, per mol of enzyme (molecular weight, 48 400). Methylation analysis of cellobiohydrolase glycopeptides indicates an average carbohydrate chain length of two residues. Alkaline borohydride treatment of cellobiohydrolase C released neutral carbohydrate which is bound through an average of 16.7 O-glycosidic linkages to serine and threonine per molecule of enzyme. Glucosamine was not released from the protein by alkaline treatment. Analysis of alkaline borohydride-released carbohydrate by high pressure liquid chromatography demonstrated that an average enzyme molecule contains 8.8 mono-, 1.8 di-, 4.6 tri-, 1.2 tetra-, and 0.4 pentasaccharide chains. The linkages between the neutral monosaccharides are (1 leads to 6) as shown by gas chromatography - mass spectrometry of partially methylated residues. The (1 leads to 6) linkage is consistent with the stability of the linkages to alkaline conditions and the destruction of all neutral carbohydrate by periodate. Action of alpha-mannosidase indicates that some oligosaccharide chains contain alpha-mannose as the terminal residue.


Phospholipids of Semliki Forest virus grown in cultured mosquito cells. The phospholipids of Semliki Forest virus grown in mosquito cells (Aedes albopictus) were analyzed radiochemically. The ratio of 32P-labeled phospholipids to total 32P-label in the virus grown in mosquito cells equilibrated with radiophosphorus was 0.558 +/- 0.021. This value was similar to the lipid phosphorus: total phosphorus ratio (0.539 +/- 0.025) of the virus grown in the BHK cells. It is concluded that an average virion of the two types of Semliki Forest virus contains approximately the same number of phospholipid molecules. Phosphatidylethanolamine (62%), phosphatidylcholine (14%), phosphatidylserine (10%) and the ethanolamine analogue of sphingomyelin, ceramide phosphoethanolamine (9%) were the principal phospholipids in the mosquito cell-grown virus. Comparison with the lipids of virus grown in hamster cells (BHK cells) revealed that two-thirds of the polar structures were dissimilar. Surface labeling with formylmethionyl [35S] sulfone methylphosphate suggests that a relatively large fraction of ceramide phosphoethanolamine is located in the outer half of the lipid bilayer of the viral membrane.


Translation of tubulin messenger ribonucleic acid. Tubulin messenger RNA has been partially purified from embryonic chick brain. This messenger has been shown to be polyadenylated and capable of directing tubulin synthesis in an heterologous cell-free protein synthesizing system. Phosphocellulose fractions of IF-3 derived from embryonic leg muscle or brain were tested for their effect on tubulin and myosin synthesis in vitro. Phosphocellulose fraction four from either tissue source stimulates tubulin synthesis three fold. Myosin synthesis is enhanced significantly only by the muscle subfraction. This result suggests the existence of specific factors in muscle for the translation of the myosin messenger.


Primary cultures of rat aortic media: a growth stop phenomenon different from contact inhibition. Cultures have been made from explants of thoracic aortas to study the growth pattern of aortic mediacytes. Explants from aortas of eight rats, aged between seven to eight weeks, were seeded. Three parameters were measured weekly from the second to the nineth week: the surface of the culture (S); the relative increment of this surface (delta S/S) and the number of 3H-thymidine labelled cells by the unit surface (n chi S-1) after autoradiography. The surface of primary culture, in relation to time, has roughly the shape of a sigmoidal curve. Growth is continuous until the fifth week and reaches a plateau beyond that time. The two other parameters decreased regularly during the first phase to attain a minimum at the beginning of the plateau-period; however new cells in the S-phase are still found in this second period.


[Changes in the incorporation of labelled amino acids into proteins and homogenates of the brains of rats that have suffered acute hypoxia in the antenatal period]. The authors studied C14-leucine and S35-methionine incorporation into the brain tissue homogenates and protein from different parts of the brain of rats subjected to intrauterine hypoxia. Depression of protein synthesis in certain brain structures, particularly in the hyppocampus was observed alongside with the stimulation of the amino acid incorporation into proteins of the other parts of the brain. Changes of the amino acid penetration into tissue homogenates fialed to correlate with the rate of their incorporation into proteins in separate structures of the brain. Experimental results pointed to disfunction in the protein metabolism intensity and in the blood-brain barrier system occurring during the late ontogenesis in rats surviving the intrauterine hypoxia.


Feedlot manure top dressing for irrigated pasture: good agricultural practice or a health hazard? Top dressing a spray-irrigated pasture of orchard-grass with 125 t/ha of overwintered beef feedlot manure almost doubled the yield of dry forage: 6353 kg/ha vs. 3578 kg/ha for the plots receiving no manure. Even at this rate of application, the manure did not contaminate the irrigated grass with enteropathogenic bacteria after irrigation. When the grass became contaminated through the use of fecally polluted irrigation water, the fecal coliforms, indicator organisms with survival characteristics similar to the salmonellae, were effectively eliminated from the grass after exposure to 65 hr of bright sunlight.


New protein sources.

New protein sources. The question whether there is a real need for more protein is first critically reviewed and the two main ways of making more protein available are then exposed. They comprise the more efficient use of the protein already available and the synthesis of new protein. The possibilities offered by the oilseeds are then briefly expounded and the difficulties encountered in their practical application are evaluated. The texture meat-like products based on extruded soya and the more sophisticated spun fibers are mentioned. Protein synthesis using yeast, bacteria and algae as microorganisms is then described. The single-cell protein (SCP) products obtaine on different substrates (paraffins, alcohols or inorganic substrates) are evaluated as regards their general composition, amino acid content and nutritive value. The problems of wholesomeness and tolerance are briefly touched upon and the development of three generations of SCP products is envisaged, each having a higher degree of purity and being more suited as a food. Finally the prospects of SCP as human food are discussed.


[Significance of the endodermal sinus tumor (Teilum) and of simplified teratoma of vitelline determination]. The histogenesis of yolk-sac tumors has been explained by a selective cloning for extra-embryonic entoblast amongst totipotent carcinoma stemcells. The diverses appearances of the tumor growths are expressed mainly in the range of cyto-differentiations of entoblastic tissue rather than in their ability to form structures which mimick the yolk-sac. The process is clearly apparent in embryoids which are becoming disorganized and during the course of experimentally induced mouse parietal endodermal carcinoma. The latter's appearance is strong evidence that the laws of specificity are obeyed. Human tumors should be analyzed through human embryology. Some paradoxical aspects emerge occasionally due to the angiogenesic capabilities of the neoplastic vitelline tissue, and to the correlations of this tissue with the stromal vascular response.


Assessing inter-rater reliability for rating scales: resolving some basic issues. This paper extends the recent work of Hall (1974) by presenting the minimal sample sizes and the specific linear agreement weights required for assessing the reliability of rating scales commonly used in neuropsychiatric and other clinico-medical settings. The weights are shown to vary as a function of (a) whether or not the rating scale contains a point of 'absence', and (b) the number of ordinal points on the scale.


The urethral pressure profile recorded by means of CO2-perfusion at high flow rates. The urethral pressure profile (UPP) is recorded by CO2-perfusion of the urethra at a rate of 120 ml/min. The curves are reproducible. Their features are practically identical with the shape of profiles written by liquid perfusion. The curves are absolutely calibrated. High flow perfusion and calibration make it possible to compare CO2-curves with each other and even with graphs executed by other methods.


Regional variations in need for and provision and use of child health services in England and Wales. An analysis of indicators of the need for and provision and use of child health services in the 15 pre- 1974 hospital board regions in England and Wales showed that need and provisions were badly matched. There was a high degree of correlation between the indices within each of the three groups, indicating that a region with a small provision in one area of child health services would tend to have few resources in other areas also. Statistics on the use of services relate more to the provision of those services than to the need for them. Regions with large resources will justify these resources by claiming that their use statistics indicate needs, whereas they really indicate met demands. It is more important to identify demands and needs that are not being met.


Gonorrhoea in women and exposure to risk. Data are presented on the characteristics of women with newly diagnosed gonorrhoea who attended Lydia Clinic, St. Thomas' Hospital, during a 6-month period. Although gonorrhoea in women is largely asymptomatic, there was strong circumstantial evidence to suggest that some women had attended because they had been exposed to risk. The proportion of women thus motivated was largest among those women who had attended a clinic for sexually transmitted diseases before--in which up to 40 per cent. of women had apparently attended entirely of their own accord. Women born in the West Indies differed from their counterparts born in the United Kingdom in three respects: they were younger, recorded fewer contacts, and referred themselves less frequently to the clinic for a first visit. Implications for health education and for future research are discussed.


Neuroanatomic projections related to biting attack elicited from ventral midbrain in cats. A single electrode was implanted in each of ten cats at a point in the ventral midbrain from which nonaffective biting attack on a rat could be elicited by electrical stimulation. A lesion was then made which was just large enough to eliminate the elicitation of attack at suprathreshold intensities from that electrode. After post-lesion survival times of 3-14 days the cats were sacrificed, and the degeneration resulting from the lesions was followed with the use of modified Nauta silver stains. Four additional cats were used as anatomic controls. Degenerating fibers were observed to descend bilaterally through the midbrain, pontine, and medullary tegmentum to the vicinity of the principal sensory and motor nuclei of the trigeminal nerve. There was, in addition, evidence of degenerating terminals within the nucleus of the facial nerve and the spinal nucleus of the trigeminal nerve. Of particular note was the observation that the degenerating fibers in the region of the nucleus of the spinal tract of the trigeminal nerve terminated in glomeruli in the rostral portion of the nucleus. Degenerating fibers ascending from the lesion were found to course along the medial forebrain bundle into the hypothalamus and the midline thalamus in a pattern very similar to that previously demonstrated after lesions of biting attack sites in the hypothalamus. The role that the neural pathways associated with ventral midbrain attack sites might play in the mediation of behavior patterns which are elicited during attack stimulation was discussed and it was concluded that the demonstrated neural pathway could provide a cogent explanation for some of the properties of centrally elicited attack behavior.


Comparison of changes in tryptophan and serotonin in regions of the hamster and the rat brain over a twenty-four hour period. Groups of male golden hamsters and Sprague-Dawley rats were sacrificed at 4-h intervals over a 24-h period. Tryptophan and serotonin (5-HT) were measured in the telencephalon and brain stem and tryptophan was measured in serum. Highly statistically significant changes in tryptophan and 5-HT content were observed over the period of the day. Generally the changes were more clearly defined and were significant to a higher statistical level in the hamster than in the rat. Statistically significant changes were also observed in serum tryptophan. In the hamster the daily changes in serum tryptophan were coincidental with similar changes in tryptophan and 5-HT in the brain stem and tryptophan in the telencephalon. On the other hand, the changes in 5-HT in the hamster telencephalon were not well correlated with changes in tryptophan and serum tryptophan.


Impaired retention of visual discriminated escape training produced by subseizure amygdala stimulation. These experiments examined the effects on memory of posttrial, subseizure, electrical stimulation of the amygdala. Rats were trained in a visual discriminated avoidance Y-maze. Each animal received 6 tirals on the training day. Retention, tested the following day, was measured both by the number of correct choices on the first 6 retraining trials and by the number of trials to a criterion of 5 of 6 correct choices. If administered 2 min, 1 h, or 4 h, but not 10 h, after training, bilateral amygdala stimulation significantly impaired retention as measured 24 h after training. In a second experiment, rats received unilateral amygdala stimulation in order to examine better the anatomical localization of effective stimulation sites. The unilateral stimulation was administered either 2 min, 10 min, 1 h, or 4 h after training. The behavioral procedures were the same as those used in the first experiment. For animals stimulated 2 min after training, the optimal stimulation region was one which extended rostrally from the ventrolateral portion of the basomedial nucleus to the dorsomedial region of the amygdala near the stria terminalis and nucleus centralis. For animals stimulated after a 10 min training-treatment interval, this amygdala region was not an effective stimulation site. However, in these animals, stimulation of the basolateral nucleus impaired later retention. Unilateral, posttraining amygdala stimulation administered 1 or 4 h after training did not appear to produce retention deficits. The findings of these experiments thus indicate that posttrial unilateral or bilateral amygdala stimulation impairs retention of discriminated avoidance training. Furthermore, the specific amygdala site at which posttrial stimulation impairs later retention varies with the training-treatment interval.


Patterns of gastric electrical and motor activity in miniature pigs. Gastric myoelectrical and mechanical activity was recorded in miniature pigs using chronically implanted electrodes and strain gauge force transducers. Semiautomated methods were devised to obtain quantitative evaluations of the electrical and mechanical parameters measured in fasted and fed animals. The patterns of gastric myoelectrical activity in pigs were, on the whole, similar to the patterns described in dogs, including regular cyclic control activity and spike response activity associated with muscle contraction. However, several points were peculiar to the species studied: conduction velocity of pacesetter potentials increased only moderately in the antrum; tachygastria never occurred in the experiments; in response to a standard meal, the frequency of pacesetter potentials gradually increased; mechanical activity proceeded at its maximal force immediately after feeding and for a long period; no evidence of 'migrating electrical complexes' was found in the stomach during fasting. The 40-min period following administration of a test meal appeared especially suitable for pharmacological or physiological experiments in which inhibitory factors are to be tested on the stomach.


Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India. In Gujarat, India, 6718 industrial workers, over 35 years of age, with oral leukoplakia (confirmed clinically and microscopically), were studied. After 2 years, 4762 (71%) of the individuals were re-examined. The buccal mucosa was the most common site of occurrence; 98.3% of these individuals had oral habits, with smoking alone or smoking in combination with "pan" or "supari" chewing accounting for 74.9% of the habit forms. Six individuals (0.13%) with oral leukoplakia developed oral carcinomas within 2 years. This incidence of malignant transformation was equivalent to 63/100,000 per year, which far exceeds that of new oral cancers expected even in high-risk populations. While 57.3% the leukoplakic lesions remained unchanged during a 2-year interval, 31.6% disappeared and 11% had an altered appearance. This study confirmed the precancerous nature of oral leukoplakia.


Treatment of malignant gliomas and brain metastases in adults with a combination of adriamycin, VM 26, and CCNU. Results of a phase II trail. Forty-three patients with inoperable or recurring malignant gliomas, and 30 patients with multiple recurring brain metastases were treated with a combination of Adriamycin (45 mg/m2) and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m2 for 2 days) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) (60 mg/m2 for 2 days). These cycles of treatment were repeated as soon as the hematologic restoration was complete. The treatment was well tolerated and the clinical condition of 31 of 43 glioblastoma patients improved during the 2 months after the beginning of the treatment. Six of eight patients with breast cancer metastases, one of 13 with bronchial cancer matastases, and three of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results obtained revealed the following characteristics: 1) This combination had a low degree of efficiency in the treatment of metastases to brain, except for breast cancer metastases; 2) there was no complete correlation between the clinical results observed and the cinegammagraphic developments; 3) the results obtained were similar, independent of the initial localization; and a 6-month median survival period was established, with 10 patients now in a state of apparently complete remission, 180 to 506 days after beginning of the treatment.


Angiomatosis retinae. An ultrastructural study and lipid analysis. A nonfamilial case of agiomatosis retinae (retinal hemangioblastoma) was studied by electron microscopy. In addition to the three major types of cells previously identified within the tumor (endothelial cells, pericytes, heavily lipidized stromal cells), fibrous astrocytes in different stages of lipidization were also found. The endothelial cells were fenestrated, providing the basis for the extravasated exudate that is characteristic of the tumor. The pericytes were completely surrounded by casement membranes and displayed no significant lipidization; in a cellular plaque of vasular tissue at the base of the lesion, however, some of the multilaminar pericytes showed evidence of early smooth muscle differentiation. The stromal cells contained abundant lipid vacuoles and a few organelles, and exhibited granular degeneration of cytoplasmic filaments between the lipid vacuoles. There was spotty basement membrane formation where the stromal cells abutted on the vascular elements. No interconversion could be demonstrated among the endothelial cells, pericytes, and stromal cells. A source for the stromal cells was discovered in the early lipisization of fibrous astrocytes. Analysis of the extracted lipid from the tumor by means of infrared spectroscopy, lipid chromatography, and x-ray diffraction disclosed that the lipid was mostly cholestrol stearate, a plasma lipid. It is suggested that in the retinal lesions the leaky (fenestrated) capillaries of the tumor allowed the passive imbibition of plasma lipid by the fibrous astrocytes, leading to their gradual transformation into the fully lipidized stromal cells.


Protein cross-linking properties of the antitumor agent inosine dialdehyde (NSC-118994). Inosine dialdehyde (IdA), a new antitumor agent presently undergoing clinical evaluation in man, possesses two aldehyde groups that form stable complexes with a variety of biologic molecules containing amino groups. Complex formation of IdA with lysine, glycine, histidine, or bovine serum albumin (BSA) greatly reduces the cytotoxicity of IdA against L1210 leukemia in vitro. Complexes of IdA and BSA exhibit molecular weights ranging from 69,000 to greater than 800,000 as determined by Sephadex G-200 gel filtration, indicating that both aldehyde groups of IdA are functional and can cross-link protein molecules. The cross-linking of plasma proteins and the cross-linking of glycine to BSA were also observed. No interaction of IdA with nucleic acids, nucleic acid bases, or nucleosides was detected. The dialdehyde derivatives of other nucleosides also possessed cross-linking properties.


The follicular prolactin cells of the primitive teleost engraulis japonica. The elopiform teleost Engraulis japonica was used for a light and electron microscopical study of the follicle epithelium in the rostral pars distalis of the pituitary. In this species, which has one large follicle in the anterior hypophysis, there is no persistent orohypophysial duct in postmetamorphic stages. The apical pole of the prolactin cells is almost completely overlaid by a surface layer of flattened epithelial cells with a thick glycocalyx. The prolactin cells reach the follicular lumen through "pores" in this cell layer and at the site of the pore the prolactin cells bear unusual specializations consisting of one cilium, several tall microvilli, and a mass of granular material. Prolactin release takes place at the basal pole of the cells.


Ultrastructural studies on the epithelia of the olfactory organ of cyprinodonts (Teleostei, Cyprinodontoidea). The epithelia of the olfactory organ of two cyprinodontoid fish species were studied both by transmission and scanning electron microscopy. The relatively flat floor of the organ is covered by sensory and nonsensory epithelia. The latter is distributed in the form of bands or ridges separating distinct areas of sensory epithelium. Differences between the olfactory organs of the two species investigated related only to the topography and quantitative distribution of the epithelia. Their ultrastructural features are very similar. The nonsensory stratified squamous epithelium contains numerous goblet cells and surface cells provided with microridges. A hypothetical function of the microridges is discussed. The sensory epithelium consists mainly of basal, supporting, and two types of sensory cells, i.e., ciliated and microvillous receptor cells. The cilia exhibitapredominant 9+0 microtubule pattern. Both epithelia are covered by a mucus layer in which all surface structures seem to be embedded. The possible nature, origin, and movement mechanisms of the mucus are discussed.


Fine structure and cytochemistry of specific granules in the lamprey atrium. Fine structural and cytochemical studies were performed to examine the nature of three types of specific granules found in the atrium of lamprey; specific granules of the atrial muscle cell (ASG), interstitial cell granules (ICG) and endocardial endothelial granules (ESG). Ultrastructurally, ASG and ICG appeared quite similar in size, shape and electron opacity, while ESG were much larger and less dense in opacity than the other two. None of the granules showed positive DAB reaction or acid phosphatase reaction. Only ICG revealed positive chromaffin reaction, which agreed with formaldehyde induced green fluorescence along the atrial lumen. Phosphotungstic acid at low pH stained ICG and ASG strongly positive, and ESG weakly positive. Pronase treatment in Epon sections for 24 h digested ASG alone, whereas in glycol-methacrylate embedded sections, ESG were digested first, ASG were digested thoroughly after 30 min, but ICG were not digested completely after 90 min. From these results it can be concluded that the three types of specific granules have different constituents. ESG consist of protein with some polysaccharides; ASG are composed of protein carbohydrate complexes and lack catecholamines; ICG contain catecholamine as well as protein carbohydrate complexes.


On the yolk sac of the cat. Endoderm and mesothelium. The ultrastructure of feline yolk sacs from 11 stages between the 14th and the 66th day is described with reference to the endoderm and the mesothelium; supplementary histochemical and cytochemical studies are included. Despite the absence of yolk, the endodermal epithelium shows a high degree of differentiation and activity, especially in the period between the 25th and the 38th day. Large stacks of RER, abundant SER, mitochondria enveloped by RER cisternae, and a peculiar type of lysosome are the most prominent organelles. Acid phosphatase, succinic dehydrogenase and NAD- and NADP-diaphorases are found with high activity, whereas the 17beta-hydroxysteroid dehydrogenase assay stains the endothelium only moderately. Indications of reabsorption are less marked. In view of the apparent immaturity of the liver parenchymal cells at this stage, the yolk sac endoderm of cat is suggested to act as an important extraembryonic site of biosynthesis. As preliminary results of a chemical analysis show that the yolk sac fluid has nearly no nutritional value, the substances synthesized are believed to be transported directly to the fetus. The mesothelium shows relatively few alterations over the period studied, is less rich in organelles and is obviously far less active than the endoderm.


Studies on the ovotestis of the slug Agriolimax reticulatus (Müller). The ovarian oocytes of Agriolimax reticulatus (Müller) have been studied by light and electron microscopy and electron cytochemistry. The development of the oocyte in the ovotestis may be divided into three stages. During Stage I the oocyte cytoplasm contains mainly ribosomes and also strands of endoplasmic reticulum, scattered mitochondria and Golgi systems. The nucleus contains both a paranucleolus and an eunucleolus. By Stage II the oocyte has enlarged, especially in a plane parallel to the basemend membrane. In addition to the above mentioned organelles, the cytoplasm contains lipid, glycogen and early yolk platelets. During Stage III, the oocyte continues to enlarge, but mainly in a plane perpendicular to the basement membrane. A considerable degree of cytoplasmic differentiation has also taken place. The plasma membrane of the oocyte has become specialized with the appearance of a polysaccharide-rich glycocalyx, microvilli and pinocytotic tubules. Elsewhere, much of the background cytoplasm, containing Golgi-derived, polysaccharide and acid phosphatase-rich multivesiculate bodies, lipid and glycogen, is sequestered by smooth membranes and ultimately fuses with the growing yolk platelets. The nucleus contains an amphinucleolus, characteristic of many gastropods. The findings of this study are discussed in relation to results from other studies on oogenesis.


Transformation of cytoplasmic actin. Importance for the organization of the contractile gel reticulum and the contraction--relasation cycle of cytoplasmic actomyosin. (1) Within the low viscous flowing endoplasm of Physarum polycephalum a considerable amount of actin is in the non-filamentous state. This can be demonstrated by applying poly-L-lysin to surface spreads of native protoplasm. (2) It has been shown that in protoplasmic drops the endoplasm-ectoplasm transformation is accompanied by an actin polymerization from the non-filamentous state to F-actin. (3) The actual state of the labile G-F-actin equilibrium determines the varying consistency (viscosity) of the cytoplasm. (4) Increasing viscosity can be interpreted as being brought about by a) shifting of the G-F-actin equilibrium to the filamentous side, and (b) increased myosin-mediated binding sites between actin filaments. (5) Polymerization and depolymerization processes are involved in the rhythmically occurring contraction-relaxation cycle of cytoplasmic actomyosin in Physarum. (6) Cytoplasmic actin and myosin represent the architectural proteins of the contractile gel reticulum in eukaryotic cells. (7) The importance of the regulation of actin polymerization as a basic control mechanism of the eukaryotic cell is discussed.


Dictyostelium 17S, 25S, and 5S rDNAs lie within a 38,000 base pair repeated unit. Mapping with the restriction enzymes Sal 1 and R1 has generated a picture of the organization of Dictyostelium ribosomal DNA. The DNA which codes for 17S and 25S ribosomal RNAs is located within a stretch of repetitive DNA at least 38,000 base pairs long. This repeated unit includes 5S DNA, linked to 25S DNA. Two techniques were especially useful in the mapping: "cloning" 14S + 25S DNA on the plasmid pMB9 to amplify individual R1 fragments, and digesting DNA with R1 in the presence of the antibiotic distamycin A to produce specific partial digestion products.


Release of RNA--DNA-protein complex during differentiation of the water mould Allomyces arbuscula. A correlation between release of a nucleic acid protein complex into the external medium and sporangial differentiation was found. Conditions preventing differentiation also stopped the release. Lethal lysis is not involved in this release process. Extracellular nucleic acids are very heterogenous, consisting of nucleotides as well as acid-precipitable nucleic acids. RNA was found to be associated with proteins and a hetero-duplex RNA--DNA associated with this nucleoprotein. Some speculations are presented about possible correlation between the release of nucleoprotein complexes and the intracellular events of differentiation.


Cell specific activity of trehalose-6-phosphate synthetase during differentiation of Dictyostelium discoideum. Trehalose-6-P synthetase activity was low at the beginning of the life cycle of Dictyostelium discoideum, reached maximum activity at 20 h, and decreased at late sorocarp. Enzyme activity in developing spore cells increased 10-fold during differentiation from myxamoebae (0 h) to the culmination stage (20 h) and decreased slightly at sorocarp (24 h). Activity was similar in spore cells at the apex of the stalk. The activities in the stalk cells were dependent upon their position in the developing stalk. There was a decreasing gradient of activity from the apex to the base of the stalk.


Clones of Friend leukemia cells: differences in karyotypes and responsiveness to inducers of differentiation. Several clones of Friend leukemia cells have been established which differ in their chromosome composition. These cells also vary with regard to their responsiveness to DMSO, whereas all are responsive to butyric acid. Hence, there appears to be independent assortment of the ability of a cell line to respond to DMSO and to butyric acid, suggesting a different mechanism of action for each agent. Further, individual Friend cells possess the ability to simultaneously contain chloroacetate esterase and heme--two biochemical properties which have previously been believed to be mutually exclusive.


A deuterium nuclear magnetic resonance study of the condensing effect of cholesterol on egg phosphatidylcholine bilayer membranes. I. Perdeuterated fatty acid probes. Deuterium nuclear magnetic resonance quadrupole splittings Dq and the related acyl chain segmental order parameters Smol have been determined for perdeuteriostearic acid intercalated as a molecular probe in the lamellar liquid crystalline phase of egg yolk phosphatidylcholine-cholesterol-water mixtures. The 2H NMR data show that cholesterol induces a high degree of order in the acyl chains of the phospholipid while maintaining the general profile of high order near the head group and relatively low order in the middle of the bilayer. This results in a pronounced thickening of the bilayer and concomitant decrease in the average molecular area of the fatty acyl chains. The giometrical changes in the bilayer due to cholesterol are discussed in terms of trans-gauche isomerization in the fatty acyl chains. The picture of the condensing effect revealed by 2H NMR is consistent with that from previous X-ray diffraction experiments. No evidence for a specific complex between cholesterol and phosphatidylcholine is apparent. The condensing effect of cholesterol is attributed to interaction between the fatty acyl chains and the rigid steroid nucleus, and to solvation of the 3beta-hydroxyl group at the aqueous interface.


Subaortic obstruction after the use of an intracardiac baffle to tunnel the left ventricle to the aorta. Postoperative hemodynamic studies in five patients document subaortic obstruction after surgical repair utilizing an intracardiac baffle to establish continuity between the left ventricle and the aorta. Four of the patients had a Rastelli procedure for D-transposition of the great arteries with a ventricular septal defect and pulmonary stenosis; one patient had repair of double outlet right ventricle with a ventricular septal defect and pulmonary stenosis. The left ventricular outflow was shown to be a long narrow tunnel by angiography in four of five patients and by echocardiography in one patient. Resting aortic peak systolic pressure gradient ranged from 10 to 42 mm Hg (mean 24). The obstruction was localized to the proximal end of the left ventricule to aorta tunnel (i.e., at the site of ventricular septal defect) in five patients. One patient with a gradient of 42 mm Hg has angina and decreased exercise tolerance. Subaortic obstruction is a newly described sequelae after the Rastelli procedure for transposition or repair of double outlet right ventricle. The obstruction may be hemodynamically significant and should be searched for at postoperative cardiac catheterization.


Current status of porcine heterograft prostheses: a 5-year appraisal. Between 1970 and 1975, 234 porcine heterograft valve prostheses were implanted in 193 patients with 12 operative (6%) and 21 late deaths (11%). Detailed hemodynamic studies were made 6 months to 1 year following operation in 72 patients. Mean atrioventricular (A-V) diastolic pressure gradients averaged 5.2 mm Hg for 29 mm heterografts and 2.3, 2.5, and 2.7 mm Hg for 31 mm, 33 mm, and 35 mm heterografts, respectively. In 10 patients with aortic prostheses peak systolic gradients averaged 16 mm Hg at rest (range 0-26) but increased to 70 mm Hg during exercise (range 20-125). Anticoagulants were not used except when intracardiac clot was present at operation. There were 12 systemic arterial emboli, all with mitral prostheses and low cardiac output; nine patients were in atrial fibrillation and three were in sinus rhythm. Three patients evidenced late tissue failure. Hydraulic function in the A-V position is excellent: prosthetic valve size is not limited by tertiary orifice and A-V anulus accepts large prosthesis. The patient's anulus is the determinant of aortic prosthesis size; heterograft internal diameter to outside diameter ratio is suboptimal and hydraulic function of the aortic prosthesis is marginal. In our clinical practice we consider the performance characteristics of currently available valves in relation to the individual patient's priorities to select an appropriate prosthesis.


Actuarial comparison of Hancock porcine and prosthetic disc valves for isolated mitral valve replacement. From July 1970 through December 1974, 109 patients underwent isolated mitral valve replacement (MVR). A Harken prosthetic disc valve (DVR) was used in 53 patients and glutaraldehyde-preserved Hancock porcine xenograft (PVR) in 56 patients. The functional class, distribution of mitral valve pathology, and incidence of atrial fibrillation were similar in both groups. There were no operative and three (5.5%) late deaths in the PVR group and two (3.8%) operative and ten (19.5%) late deaths in the DVR group. Anticoagulants were not used in the PVR group; there were 3 nonfatal emboli (10%), all occurring in  patients with atrial fibrillation and large left atria. Although anticoagulants were used there were 14 emboli (five in patients who died, nine nonfatal) in the DVR group (26.4%). In our experience, there is a significant reduction in morbidity and mortality, primarily from a reduced risk of thromboemboli, if a porcine valve is used for MVR. Anticoagulants should be used in patients with atrial fibrillation and enlarged left atria regardless of the type of valve used.


Biological rhythm of cell-mediated immunity in man. The biological rhythm of the spontaneous lymphocyte transformation and the lymphocyte response to phytohaemagglutinin (PHA), concanavalin A (Con A) and purified protein derivative of tuberculin (PPD) was studied in six healthy male volunteers. The count of peripheral blood lymphocytes was increasing from 08.00 until 02.00 hr. The level of plasma cortisol was highest at 08.00 hr and lowest at 20.00 hr. The spontaneous lymphocyte transformation showed a biphasic cycle during the day; the peak values were observed at 08.00 and 20.00 hr and a significant depression was found at 14.00 hr. The response of peripheral blood lymphocytes to PHA and Con A varied inversely with the level of plasma cortisol. The PPD response was lowest at 08.00 hr, but the highest value was observed at 02.00 hr. No significant day to day variation was found in any of the parameters studied.


Genetic study of amobarbital elimination based on its kinetics in twins. Following the intravenous administration of 125 mg amobarbital sodium in 7 pairs of dizygotic and 7 pairs of monozygotic twins, the time-course of plasma concentrations was observed. The number of detectable compartments varied from subject to subject but was consistently 1 or 2 or 3 within a given individual. The terminal slope of the semilogarithmic concentration-time plot (corresponding to biologic half-life of 22.8 hr) did not represent the elimination rate constant even in persons with apparently single-compartmental characteristics. The redistribution of amobarbital was rapid in comparison with its elimination. The rate of the latter (characterized by kel = 0.051 hr-1, plasma clearance = 37.7 ml/min) could be closely identified with the rate of metabolism. The twin data showed that genetic control was exerted on kinetic parameters characterizing the rate of amobarbital elimination and, therfore, the rate of its metabolism. Correlation analysis suggested that this control was independent of size factors, which were themselves substantially heritable. The genetic analysis of twin data included, in addition to intracelass correlations and Holzinger's H factors, newly developed lower (and upper) bounds of the broad-sense heritability. In pharmacogenetic studies, assessment of model-independent kinetic parameters, such as plasma clearance with or without adjustment for body weight, is recommended.


[Fetal alcohol syndrome (author's transl)]. The fetal alcohol syndrome was observed in four girls aged 1 2/12 to 9 2/12 years, two of whom were sisters. Three of the children are older than all others previously described as having this syndrome. The signs consist of a decrease of body length and weight beginning at birth, microcephalus, marked decrease of intelligence and narrowing of the palpebral fissure. Frequently congenital cardiac defects are found and sometimes anomalies of the genitalia and other malformations. Experience so far indicates a causal relationship between considerable alcohol abuse of mothers during pregnancy and intra-uterine fetal damage. The prognosis is poor; in severe cases of chronic alcoholism interruption of pregnancy should be seriously considered.


[Glisoxepide treatment in maturity-onset diabetics (author's transl)]. Patterns of blood glucose, serum insulin and non-esterified fatty acids (NEFA) were measured over a period of eight-and-a-half hours in eleven maturity-onset diabetics receiving 8 mg glisoxepide in the morning and 4 mg in the evening (while on a standard diet). The effects of administering the tablets in the morning with breakfast were compared to those on administering the drug half-an-hour (five patients) or one hour (six patients) before breakfast. Although there was a slightly earlier increase in serum insulin when tablets were taken half-an-hour or an hour before breakfast, different times of administration did not significantly affect the blood glucose or NEFA pattern. In particular, the extreme rise in blood glucose levels after the first breakfast could not be avoided.


[Erysipelothrix endocarditis (author's transl)]. Following erysipeloid a 46-year-old man fell ill with septicaemia and endocarditis. Treatment with high doses of antibiotics could not prevent his death. Infection with Erysipelothrix rhusiopathiae in man occurs through a skin lesion and only rarely leads to spreading of the agent in the body presenting as arthritis, meningitis, or endocarditis. Erysipelothrix endocarditis is a severe disease leading to widespread destruction of the involved cardiac valves. The aortic valve is most commonly involved. 16 out of 28 patients with erysipelothrix endocarditis reported in the literature died, eleven of them despite treatment with antibiotics.


[Treatment of infertile women with epimestrol (author's transl)]. 155 patients have been treated with epimestrol during 593 menstrual cycles in a daily dosage of 5, 10 or 2.5 mg from the 1st to the 10th or from the 5th to the 14th day of the cycle. 143 patients with secondary amenorrhoea, anovulatory cycles, ovulatory oligomenorrhoea, corpus luteum insufficiency, and normal cycles received epimestrol after an average period of 2.4 years of involuntary infertility. The pregnancy rate was 21% (n = 30), the spontaneous abortion rate 13% (n = 4). Twelve further patients not seeking pregnancy were treated with epimestrol because of secondary amenorrhoea and (or) anovulatory bleeding. The results were as follows: 1) In eugonadotropic secondary amenorrhoea 8 out of 12 patients ovulated, 5 out of 10 patients wanting children became pregnant. No patient with hypogonadotropism ovulated. 2) Out of 25 patients with anovulatory  cycles or bleeding 13 ovulated and 4 became pregnant. 3) 17 out of 68 oligomenorrhoeic patients became pregnant. 4) In 12 out of 24 patients with corpus luteum insufficiency the hyperthermic phase improved and four patients became pregnant. 5) In 12 patients without anomalous cycles these remained unchanged and there were no pregnancies. 6) No side effects could be observed.


[Metapramine: antidepressant and psycho-stimulant]. Metapramine is a new antidepressant drug. A tricyclic molecule gives it a novel activity in so far as its thymoanaleptic and, at the same time, psychostimulating actions are concerned. Quick acting, metapramine has a very interesting peculiarity: its large tolerance which seems to be related to a no-anticholinergic effect.


Circulating placental lactogen levels in dairy and beef cattle. Levels of bovine placental lactogen (bPL) have been measured in the serum of dairy and beef cattle and in the milk and amniotic fluid of pregnant animals with a highly specific radioimmunoassay. In both dairy and beef cows, serum bPL levels remain low (less than 50 ng/ml) during the first two trimesters and then rise rapidly between 160 and 200 days of gestation to a plateau. The bPL levels do not decline prior to parturition. During the last trimester, serum levels in dairy cows, 1103+/-342 ng/ml, are significantly higher than those in beef cattle, 650+/-37 ng/ml (P less than 0.01); furthermore, dairy cows having a high milk production also tend to have high bPL levels. Serum levels are almost twice as high in twin pregnancies and are not correlated with fetal sex or birth weight. bPL levels in milk and amniotic fluid from dairy cattle during the last trimester are approximately 86% and 25% of the serum values, respectively, suggesting that bPL enters these fluids by passive diffusion.


Androgens augment FSH-induced progesterone secretion by cultured rat granulosa cells. Granulosa cells have been isolated from ovaries of estrogen-treated immature intact and hypophysectomized rats, and have been maintained in culture in a chemically-defined medium. Progesterone secretion by these cells was testosterone or 17beta-OH-5alpha-androstan-3-one (DHT), progesterone secretion was low or undetectable. However, the addition of testosterone or DHT together with FSH caused a dramatic 8- to 19-fold increase over that caused by FSH alone. On the other hand, luteinizing hormone (LH) alone had no effect on progesterone secretion, but produced a small stimulation when added together with testosterone. These results demonstrate synergism between androgens and FSH in the control of progesterone secretion by granulosa cells in culture.


The uptake and metabolism of uridine by the slime mould Physarum polycephalum. 1. Uridine is taken up by microplasmodia of Physarum polycephalum via a saturatable transport system with an apparent Km of 29 muM. An intracellular concentration significantly higher than that in the growth medium is attained, suggesting that the uptake is an active process. Both deoxyribonucleosides and ribonucleosides are competitive inhibitors of the uptake of uridine. 2. In contrast, the rate of entry of uridine into surface plasmodia is a linear function of the concentration of the nucleoside in the growth medium, and the uptake is not inhibited by other nucleosides. 3. As well as serving as a source of pyrimidine nucleotides for the synthesis of nucleic acids, uridine is also catabolised by P. polycephalum. Uracil accumulates in the growth medium and there is also significant conversion of C-2 of the pyrimidine ring to CO2. The proportion of uridine subject to catabolism in surface plasmodia is less than that observed for microplasmodia.


Heterogeneity of native ribosomal 60-S subunits in Ehrlich ascites tumor cells cultured in vitro. Native large ribosomal subunits in cultured Ehrlich ascites tumor cells analyzed by high-resolution CsCl isopycnic centrifugation consist of at least two classes of particles with densities of 1.57 g/cm3 (LI) and 1.59 g/cm3 (LII), respectively. A wash with 0.5 M KCl converts LI into particles with the density of LII particles. Incubation of derived large subunits (density 1.59 g/cm3) with 0.5 M KCl wash of reticulocyte ribosomes leads to the formation of particles with the density of LI particles. A protein with a molecular weight of 57000 present in the high-KCl wash of 60-S native subunits was virtually absent in the KCl wash of 40-S subunits or polyribosomes suggesting that specific protein factors may be present on some native 60-S subunits. Possible functions of these protein factors are discussed.


The requirement for tetravalency of soybean agglutinin for induction of mitogenic stimulation of lymphocytes. The mitogenic activity of soybean agglutinin was found to depend on the presence of lectin aggregates formed in lectin preparations stored in the lyophilized state. Such soybean agglutinin preparations gave maximal stimulation of untreated pig lymph node cells and neuraminidase-treated mouse spleen cells at relatively high concentrations, ranging from 100 to 2000 mug/ml. After separation into unaggregated (divalent) and polymeric (tetra-and multivalent) fractions, it was found that the unaggregated lectin did not stimulate the cells, while the tetravalent and multivalent fractions were active and gave maximal stimulation at a concentration of 10 mug/ml. These results suggest that soybean agglutinin must have at least four sugar binding sites in order to be able to stimulate lymphocytes.


The effect of short-term culture on the sensitivity of MDAY murine tumor cells tolysis mediated by normal rabbit serum. Freshly explanted MDAY murine tumor cells are sensitive to lysis mediated by fresh normal rabbit serum. The sensitivity, which increases with the age of the tumor, is rapidly lost upon short-term culture, and takes place at 37 degrees C but not at 4 degrees C. Cellular components released into the medium during short-term culture are capable of eliciting xenogeneic antibodies that mediate complement-dependent lysis of such cells.


The relationship between storage and secretion of specific antibody by immune lymphoid cells: ultrastructural localization of anti-peroxidase antibodies in plaque-forming cells of the rabbit popliteal lymph node. The ultrastructure of antibody-forming cells (AFC) has been studied in the lymph node cell population from rabbits locally immunized with horseradish peroxydase (PO) incorporated in complete Freund's adjuvant, and the kinetics of AFC development followed from day 7 to day 18 after one injection of PO.  Identification of the AFC was done by local hemolysis assay, using carboxymethyl cellulose solidifying medium and PO-coated sheep erythrocytes. AFC were thereafter transferred by micromanipulation into a Beem capsule, fixed, treated by PO for fine ultrastructure detection of anti-PO antibodies, included, sectioned and studied by electron microscopy. It was found that the AFC were essentially of three categories: lymphocytes, proplasmacytes and plasmacytes, with (+), or without (-), intracellular antibody. The proportion of these categories varies with the time elapsed since the injection of antigen and with the plaque-forming activity of the population: lymphocytes (-) are relatively more numerous (over 30%) at the early stages of immunization (day 7). The number of plasmacytes increases with immunization. If most of them contain intracellular antibody at the early stages (up to day 9), the proportion of plasmacytes (+) decreases markedly afterwards. The cell type distribution is compatible with the idea that the lymphocytes are the precursors of plasmacytes, proplasmacytes being transitional forms, but no direct filiation scheme can actually be deduced from these experiments.


Frequency of precursor cells against the enzyme beta-galactosidase: an estimate of the BALB/c strain antibody repertoire. A method has been developed for detecting anti-beta-galactosidase antibodies after isoelectric focusing in thin layers of polyacrylamide gel. By "staining" with wild-type enzyme, all antibodies against beta-galactosidase are detected, while a subset of antibodies able to activate a mutant enzyme is detected by staining with that enzyme. Limiting dilutions of beta-galactosidase-primed or unprimed spleen cells of BALB/c mice were transferred together with antigen into sublethally irradiated syngeneic hosts. The limiting role of the precursor B cells has been judged by the analysis of the clonal distribution of galactosidase-specific antibodies in recipient sera. The frequency of anti-wild-type beta-galactosidase precursor cells was one in 0.42 x 10(6) in the primed and one in 0.93 x 10(6) in the unprimed spleen. The frequency of precursor cells for antibodies activating the mutant enzyme was one in 1.5 x 10(6) in the primed and one in 4.6 x 10(6) in the unprimed spleen. Therefore four and five times less anti-M (mutant) than anti-B (wild-type) precursor cells exist in the spleens of primed and unprimed BALB/c mice, respectively. Comparing 51 clones derived from one primed donor mouse, it was possible to demonstrate that at least 43 different mutant-beta-galactosidase-activating antibodies can be produced in one mouse. Comparing these 43 clones with 27 clones derived from another donor mouse, only one clone seemed to be common to both mice. From this the repertoire of the BALB/c strain has been estimated to consist of over 1000 different mutant enzyme-activating antibodies.


B cell tolerance induced by polymeric antigens. VI. Kinetics and reversibility of the inhibition of antibody-forming cells by antigen. Injection of mice already making antibodies to 2,4-dinitrophenylated (DNP) Ficoll with tolerizing doses of DNP-pneumococcal polysaccharide (DNP-lys-S3) markedly inhibits the secretion of anti-DNP antibodies by IgM antibody-forming cells. The present study shows that the degree of inhibition depends not only on the dose of DNP-lys-S3 but also on the duration of exposure to antigen. DNP-lys-S3 was detectable on the surface of antibody-forming cells at a time when their rate of secretion was unimpaired, thus suggesting that the inhibition involves intracellular events subsequent to the binding of antigen to the cell membrane. The inhibition was reversible if antibody-forming cells were exposed to antigen for 24 h, and then cultured for 18 h in its absence, but became irreversible if the treatment period was extended to 48 h. The relevance of this model of inhibition of lymphocyte function by antigen to possible mechanisms of B cell tolerance is discussed.


In vitro synthesis of factor B of the alternative pathway of complement activation by mouse peritoneal macrophages. Factor B of the alternative pathway of complement activation was shown to be synthesized and secreted by unstimulated mouse peritoneal macrophages. The activity of B in the culture supernatants from macrophage monolayers was detected by consumption of C3 in reaction mixtures containing supernatant and guinea pig factors C3, D and insoluble C3b. Using a monospecific antiserum, factor B in concentrated culture supernatants was shown by immunodiffusion and immunoelectrophoresis to be identical to factor B in mouse plasma and to form a characteristic complex with cobra venom factor in the presence of D. A steady rate of factor B secretion was observed for 4 days providing the medium was changed every 24 h. Cycloheximide (0.5 mug/ml), an inhibitor of protein synthesis, caused inhibition (90%) of factor B production. Incubation of culture medium containing 14C-labeled amino acids with the macrophage monolayer resulted in incorporation of radioactivity into factor B as detected by autoradiography of precipitation lines formed with anti-B antiserum; This indicated that synthesis of factor B had occurred. In the same culture supernatants the presence of newly synthesized C3 was also demonstrated.


Withdrawal characteristics following chronic pentobarbital dosing. Experiments were performed to provide a quantitative description of the barbiturate withdrawal syndrome. Physical dependence was produced in 63 cats by 'maximally tolerable' dosing with sodium pentobarbital. After 5 weeks of chronic treatment each animal was placed in an activity monitoring cage and observed closely for signs of barbiturate abstinence. Electroencephalographic monitoring of sleep--wake cycles was performed in 5 of these cats. Most withdrawal signs appeared in 12-18 h and rapidly intensified. These included signs of neural hyper-excitability that involved motor, autoncidence, severity and time course of many withdrawal signs. 26 animals (41%) died during abstinence, usually during or immediately following grand mal type convulsions. The importance of quantitating withdrawal phenomena is discussed with respect to investigation of the requirements for physical dependency production, comparison of different drug dependencies, and pre-clinical evaluation of potential treatments of sedative-hypnotic dependence.


The bradykinin potentiating activity of two pentapeptides on various isolated smooth muscle preparations. Two bradykinin potentiating peptides A-VI5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), were compared with respect to their potentiation of a number of different bradykinin effects on six isolated smooth muscle preparations. Apart from the considerable difference in effective concentrations, no essential qualitative difference was observed between these two peptides. Therefore the assumption of a different mechanism of action for the two peptides, which have a completely different structure, could not be substantiated.


Selective 6OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats. Selective large scale destruction of mesolimbic dopamine-containing terminals is produced by bilateral injection of 8 mug of 6-hydroxydopamine (6OHDA) into the nucleus accumbens septi (NAS) of rats pretreated with pargyline and desipramine (DMI). The DMI prevents the destruction of the noradrenergic innervation of the forebrain normally produced by the NAS 6OHDA lesion, without affecting the destruction of dopamine-containing neurons. The locomotor stimulation produced by the psychostimulants d-amphetamine (1.5 mg/kg) and cocaine (20 mg/kg) is blocked in rats with selective destruction of the mesolimbic dopamine system. In contrast the locomotor stimulation produced by the directly acting dopamine agonist apomorphine (1.0 mg/kg) is enhanced, which may indicate supersensitivity of the denervated dopamine receptors. These results lend further support to the view that psychostimulant-induced locomotr stimulation in rats results from effects on mesolimbic dopamine neurons. In addition, the protection by DMI of noradrenergic neurons from the toxic effects of 6OHDA is evidence that 6OHDA, as used here, destroys catecholamine neurons mainly by an uptake-dependent specific mechanism.


p-Chloroamphetamine: short and long term effects upon shock-elicited aggression. In a series of experiments the effects of p-chloroamphetamine (PCA) on shock-elicited aggression in rats were investigated. 15 min after 5 mg/kg PCA, shock elicited aggression was inhibited. 2 h to 4 weeks after PCA, fighting was facilitated. Both the inhibitory and the excitatory effects of PCA were directly related to the dose of PCA (1.5, 2.5 OR 5 mg/kg) and were blocked by pretreatment with p-chlorophenylalanine but not by alpha-methyl-p-tyrosine. PCA-increased pain thresholds 15 min after injection and then decreased pain thresholds over the next 24 h but not thereafter, even though shock-elicited aggression continued to be facilitated. The results are consistent with the idea that inhibition of shock-elicited aggression is associated with enhanced release of serotonin whereas enhancement of shock-elicited aggression is associated with serotonin depletion.


Increased rate of disappearance of serum probenecid in barbital dependent rats. Rats were made barbital dependent by administration of barbital in their drinking water. Subsequently, the rats were either not withdrawn (BN) or withdrawn from barbital for 24 h (BW-24). Before sacrifice, probenecid was administered to measure brain serotonin turnover. A statistically significant decrease in 5-hydroxyindoleacetic acid (5-HIAA) accumulation was observed in the cerebral cortex medulla pons and  midbrain. Subsequentialy, serum levels of probenecid were also measured by gas chromatography to determine if chronic barbital consumption might affect circulating probenecid. By ninety minutes following probenecid administration, serum probenecid levels in BN and BW-24 rats were significantly lower than control while a probenecid metabolite was significantly increased. The significantly reduced accumulation of 5-HIAA in brain areas of BN and BW-24 rats is probably the result of the more rapid decline of probenecid rather than a true decrease in serotonin turnover.


Experimental studies on the influence of male alcoholism on pregnancy and progeny. Chronic alcoholism was induced in male albino rats by an oral self-administration technique. Obvious signs of intoxication, withdrawal symptoms and reduced reproductive performance, as well as decreased serum glucose and serum testosterone levels, were observed in these animals. Notable differences were detected in prenatal mortality, mean litter size and sex ratio between the offspring of male alcoholic rats and the corresponding controls. In the alcohol-treated group the placental index was markedly reduced. However, the mean growth index showed no significant differences between the experimental and control groups.


Ultrastructural investigation of peripheral arterial vessels in the cortex of rats with experimental hypertension. The peripheral arterial blood vessels in the cerebrum of 36 experimental animals and 9 controls were studied by electron microscopy. In 5 rats of these renal hypertension was produced (the animals were sacrificed 3 to 15 days following the second operation). 24 animals were treated with depot angiotensin (0.02 to 2.5 mg/daily) for 3 hr up to 40 days, and 7 rats were neurotized for 1 to 41/2 months. The alterations of the cerebral vessels were distinctly different within these 3 models already in the early reactions. Thus, even in the first 14 days of the experiment with renal and angiotensinogenic hypertension alterations were observed that did never occur in the neurotized rats. There were always observed disturbances in permeability of the cerebral vessels, but they were never followed by such heavy wall insudations as usually noticed in the splanchnic vessels. The less frequent occurrence of hemorrhages and malacic processes in the rat brain is ascribed aside from the physiological properties of the brain supply, to genetic factors and the absence of arteriosclerotic burden to the vascular wall in the non-dietetically pretreated experimental animals.


[Effect of electroshock convulsions on caudate nucleus function]. In unrestrained cats, after the electro--shock seizures, the afamphetamine--indused stereotype, behavior was increased and the caudate circular response to high--frequency stimulation was facilitated. The delayed response to low-frequency stimulation of the caudate nucleus was, on the contrary, decreased. Thresholds of the circular and delayed responses to stimulation of the thalamus and capsula interna did not change in the post--seizure period. The above shifts are supposed to be due to weakening of the caudate nucleus inhibitory function resulting from the electro--shock--evoked increase in the caudate dophamine.


[Emphysematous colpitis in the late puerperium (author's transl)]. Two cases of emphysematous colpitis in the late post partum period are reported. The clinical symptoms and signs, the pathogenesis, the causes and the treatment of emphysematous colpitis in the puerperium are described.


[A rare finding at gynaecological laparotomy: ovarian pregnancy and pinworm abscess (author's transl)]. A case of concommitant ovarian pregnancy and pinworm abscess is described. The histology and the incidence of Oxyuriasis in the female genital tract are discussed. The clinical symptoms and the management of the condition are also discussed.


[Thrombotic thrombocytopenic purpura (Moschcowitz-syndrome) in pregnancy (author's transl)]. The case of a primigravida with thrombotic thrombocytopenic purpura (Moschcowitz Syndrome) is reported. The patient delivered a healthy male infant at 35 weeks gestation during a remission. The patient died at 10 days postpartum from a relapse of the disease. The special points in the differential diagnosis and treatment of thrombotic thrombocytopenic purpura during pregnancy are discussed.


[Respiratory function of mitochondria in the inner and outer layers of the dog myocardium]. The respiratory effect of dog myocardial mitochondria was studied by measuring oxygen content in a reaction chamber using Garbani electrode. 1) In normal dog mitochondria, oxygen consumption rate (QO2) in state 3 and state 4, respiratory control ratio (RCR) and ADP/O ratio were not different between the inner and outer layers when glutamate or succinate was used as substrate. 2) Thirty min after the occlusion of one of the small branches of the anterior descending artery, there were no differences in the respiratory effects between the inner and outer layers when glutamate or succinate was used as substrate. HOowever, compared with the normal dog mitochondria, ADP/O ratio, QO2 in state 3 and state 4 were lower in the outer layer and QO2 in state 4 was lower in the inner layer when succinate was used as substrate. 3) When the anterior descending branch was narrowed to decrease the blood flow to about a half, the respiratory effects were not different between the inner and outer layers when succinate was used as substrate. However, ADP/O ratio in the outer layer was lower than that of the normal dog. 4) Nitroglycerin had no effect on the respiratory effects either in vitro (1.63 X 10(-6) M, succinate as substrate) or in vivo (20 mug/kg i.v., glutamate as substrate.) 5) Dipyridamole had no effect on the respiratory effects in vivo (250 mug/kg, i.v., glutamate as substrate) but, ADP/O ratio in the outer layer was diminished in vitro (7.34 X 10(-6) M, succinate as substrate).


[Pharmacological studies of antipsychotic drug, penfluridol. 2. General pharmacological properties]. General pharmacological properties of penfluridol (TLP-607) a long-acting antipsychotic drug, were examined in experimental animals and the following results were obtained. 1) TLP-607 produced a lowering of arterial blood pressure and bradycardia but had almost no effect on respiration and peripheral blood flow. 2) TLP-607 slightly hypertension induced by dopamine, adrenaline and noradrenaline, but had no effect on hypotension induced by acetylcholine and histamine. 3) Antagonistic actions of TLP-607 on such spasmogens as acetylcholine, histamine and barium chloride were slightly stronger than those of haloperidol and chlorpromazine. 4) TLP-607 had neither ganglionic nor neuromuscular blocking action. 5) TLP-607 had a slight or no effect in the following experiments; protection against stomach ulcer, activity of ileum and uterus in vivo and in vitro, urinary volume and electrolytes excretion, and gastro-intestinal propulsion. These results suggest that TLP-607 has no striking peripheral actions in experimental animals.


[Analgesics and the kallikrein-kinin system]. The mechanism of analgesic actions of aspirin, aminopyrine and morphine was investigated in reference to the kallikrein-kinin system and the results suggested that the analgesic actions of these agents are definitely related with the peripheral kallikrein-kinin activity. The central action of kinin appears to differ from the peripheral action.


[Pharmacological studies on bamboo grass. (2) Central depressant and antitoxic actions of a water-soluble fraction (folin) extracted from Sasa albomarginata Makino et Shibata]. Folin administered showed a significant antagonistic effect to caffeine induced hyperactivity and slightly prolonged hexobarbital induced sleeping time in mice. An antitussive effect was evident only with high doses and anticonvulsant effects were not observed. A mixture of Folin with HgCl2, NaAsO2, 3CdSO4-8H2O or tetrodotoxin resulted in an apparent decrease in mortality rates. However Folin had no effect in the case of alternate administration with a poison or preadministration of Folin. As other pharmacological properties of Folin, a protective effect on induced stress ulcer in rats and an increase in acid output in pylorus-ligated rats in which aspirin was administered. Folin had no inhibitory effect on reserpine ulcer and acetic acid induced anal ulcer in the rat. Neither an increase in gastric motility nor cathartic effect was observed with Folin. In addition, Folin showed a tendency of inhibition on heat induced edema and increase of urinary vikyne and electrolytes in rats.


[Analgesic effects of Neurotropin in mice, and a comparison with analgesic effect of other drugs in SART-stressmice]. Analgesic effects of a neuroleptica "Neurotropin" (NSP) were studied in mice while the analgesic effects of other agents were studied in SART-stress mice (specific stress caused by alterating rhythm in temperature) and the results compared with those in normal mice. NSP is an extract containing many conjugated polysaccarides isolated from the skin or tissues of rabbits which had been inoculated with the living cowpox virus. (a) NSP given alone to normal mice resulted in slight analgesic effects as observed with the application of the acetic acid-, phenylquinon-writhing method or the modified Randall-Selitto method. Little effect was seen when the D'Amour-Smith was used. (b) Synergism was evident when NSP and aminopyrine or NSP and morphine were given concomitantly and the acetic acid- or phenylquinon-writhing methods were applied. (c) Analgesic effects of morphine, levomepromazine, imidazole acetic acid and particularly NSP were greater in SART-stress mice than in normal mice. With the D'Amour-Smith method, only NSP had a greater effect in SART-stress mice than in normal mice.


[Behavioral pharmacology of a new antidepressant, lopramine]. The behavioral effects of lopramine [N-methyl-N-(4-chlorobenzoyl-methyl)-3-(10, 11-dihydro-5H-dibenz (b,f) azepin-5-yl) propylamine hydrochloride] were investigated in mice and rats and compared with those of amitriptyline and imipramine. Lopramine inhibited reserpine hypothermia and haloperidol catalepsy in mice and tetrabenazine ptosis in rats. In addition the drug potentiated the effects of methamphetamine, and DOPA- or apomorphine-induced stereotypy in mice, whereas it suppressed muricide of the rat induced by either olfactory bulbectomy or delta9-tetrahydrocannabinol, similar to the responses seen with imipramine and amitriptyline. On the other hand,lopramine increased spontaneous motor activity and markedly potentiated methamphetamine hyperactivity. In contrast to imipramine and amitriptyline, lopramine failed to counteract both the lethal effect of physostigmine and oxotremorine tremor in mice, indicating that the drug had no central anticholinergic effect. Lopramine, even at such a large dose as 5,000 mg/kg p.o., caused neitherimpairment of coordinated motor activity nor muscle relaxation. It is concluded that lopramine is a new type of tricyclic antidepressant with extremely low toxicity and without central anticholinergic action.


[Inhibition of cholinesterase activity induced by pyridaphenthion]. Inhibitory effects on cholinesterase (ChE) activity in blood of the rabbit induced by pyridaphenthion(PD), an organophosphorus compound, and effects of 2-pyridine aldoxime methiodide(PAM) on this inhibition were examined. 1) Experimental results within 24 hr: An oral administration of each dose of PD(100 approximately 750 mg/kg) gradually decreased ChE activity and ChE activity value decreased to 20.5% in the erythrocytes and 21.5% in the plasma 24 hr after administration of 500 mg/kg of PD. However, this value recovered remarkably with an intravenous injection of PAM. The ChE activity value was 55.5% in the erythrocytes and 41.4% in the plasma with a single injection, and respectively 67.8% and 59.1% when PAM was injected three times. 2) Experimental results for 14 days: Following an increase of the administered dose (100 approximately 400 mg/kg) of PD, a decrease in ChE activity was apparent and a recovery to normal values was delayed. This inhibition could be ameliorated quickly with an injection of PAM. Considering that PAM does not have remarkable detoxicative effects on organophosphorus compounds which have a low toxicity, PAM appears to be a promising antidote against PD.


[Effects of lithium chloride on norepinephrine and dopamine metabolism in the rat brain]. Lithium chloride (LiCl) was injected acutely (2.4 mEq/kg and 1.2mEq/kg X 2 for 3 hr, i.p.) or subacutely (2.5 mEq/kg X 2/day for 4.5 days, i.p.) in rats, and behavioral effects, steady state levels of norepinephrine (NE), dopamine (DA) and serotonin (5HT) and the metabolism of intraventricularly administered 14C-NE and 14C-DA in the brain were investigated. Acute and subacute administratin of LiCl suppressed the spontaneous motor activity, but had no effect on the levels of NE, DA and 5HT in the brain. Acute administration of LiCl did not influence the total radioactivity and the levels of NE and its metabolites in NE metabolism, while subacute administration of LiCl increased the deaminated metabolites. In DA metabolism, the deaminated metabolites were decreased by acute administration of LiCl and the O-methylated deaminated metabolites were increased by subacute administration. From these results, it is suggested that LiCl stimulates the monoamine oxidase pathway in NE and DA metabolism and the behavioral sedative effects of LiCl are attributed to the reduced functional activity of brain NE and DA neurons.


[Effects of MS4101, a new benzodiazepine compound, on evoked potentials induced by noxious stimulation of hind legs in cats]. The effects of 10-chloro-11b-(2'-fluorophenyl)-2,3,5,6,7,11b-hexahydro-7-(2''-hydroxyethyl)benzo[6,7]-1,4-diazepino [5,4-b]oxazol-6-one (MS4101), a new benzodiazepine compound, on evoked potential in cats were examined and compared with diazepam. Though evoked potential in somatic cortex I, motor cortex I and posterior groups induced by tibial nerve stimulation were unaffected by a small dose of MS4101 (1 mg/kg) which did not influence on limbic system, the amplitude of evoked potential in midbrain reticular formation was reduced. The amplitude of evoked potential in amygdala and hippocampus induced by cutaneous nerve stimulation was reduced by MS4101 and diazepam. These two drugs had the same effect on amygdala and difference in the degree of action between these drugs was not observed. Sham rage response following head shake, circling and whine behaviour was observed by electrical stimulation of the hypothalamus. The threshold of sham rage response by raised by MS4101 and diazepam.


[Pharmacological actions of a new antihypertensive drug, olmidine, on the gastrointestinal tract]. It has been reported that dl-2-(3,4-methylenedioxyphenyl)-2-hydroxyacetamide hydrochloride (Olmidine) shows an antihypertensive action through inhibition of the adrenergic transmission. The present experiment was an attempt to investigate the pharmacological actions of olmidine in the alimentary canal of rat, rabbit and guinea pig. We found that the salivary secretion of rabbit was unaffected by olmidine at a dose of 2 mg/kg i.v., but increased by approximately 3 times that of controls with 10 mg/kg i.v.. Volume of gastric juice, concentration of free HCl, total acidity and pH of gastric juice in Shay rats were unaffected by 20 mg/kg i.p. of olmidine while volume and free HCl were significantly reduced at a dose of 100 mg/kg i.p. of the drug. The pH of gastric juice showed an evident increase to 3.33. Total acidity, however, was unaffected. Bile secretion of rat was decreased by olmidine at a dose of 100 or 500 mg/kg i.p. in a dose-dependent manner. Olmidine did not induce any lesion of gastric mucosa of rats at a dose of 200 mg/kg p.o. or less. Movement of charcoal meal in the small intestine of rats was inhibited by olmidine at doses of 20 to 500 mg/kg p.o.. Olmidine caused a biphasic response, that is contraction followed by a relaxation,in the isolated guinea pig gastrointestinal tracts. The contractile response caused by olmidine was completely inhibited by pretreatment with atropine or scopolamine and converted to one of relaxation which was unaffected by a combined treatment with phentolamine and propranolol. Contractile responses caused by transmural stimulation were significantly potentiated by olmidine, while potentiation of the contractile responses caused by exogenously applied acetylcholine was only slight in the isolated gallbladder from guinea pig.


[Effects of eserine and ouabain on the febrile reaction induced by lipopolysaccharide]. We investigated the effects of eserine and ouabain on the permeability of the blood-brain barrier (B.B.B.) as related to the febrile response induced with LPS in rabbit. Results are as follows; The febrile response induced by LPS (0.02 and 1.0 mug/kg) i.v. was suppressed by administration of ouabain (0.06 mg/kg, i.v.). Contrary to the febrile response of LPS given i.c. (10(-4) and 10(-3) mug/kg), the febrile response was not suppressed with the same dose of ouabain. The pyrogenicity of cerebrospinal fluid (CSF) withdrawn at two hours after rabbits had been injected with LPS (25 mug/kg) was suppressed by ouabain (0.06 mg/kg, i.v.). Pyrogenic response was enhanced by pretreatment with eserine (0.5 mg/kg, s.c.) given one hr before LPS (1 mug/kg, i.v.). The pyrogenicity of CSF was also potentiated to a greater extent by pretreatment of eserine than with LPS alone. In the eserinized rabbit (0.5 mg/kg, s.c.), the pyrogenicity of CSF was potentiated to a greater extent by ACh (10 mug/kg, i.v.) than by LPS (1 mug/kg, i.v.) alone. From these data, it is concluded that the inhibition of Na, K-ATPase by ouabain decreases the pyrogenicity of LPS, while the inhibition of cholinesterase by eserine enhances the pyrogenicity.


Effect of crotonaldehyde on the metabolism of Candida utilis during the production of single cell protein from ethanol. The effect of 20 low-boiling compounds on the yeast Candida utilis 49 was assessed by a screening test on agar medium. The highest toxicity was exhibited by crotonaldehyde, allyl alcohol and acrolein. Oxidation and assimilation experiments in a slightly aerobic environment showed that an increase in the level of crotonaldehyde in the medium in the range of 10--20 mg 1-1 brings about a lowering of intensity of metabolic processes in Candida utilis, suppression of ethanol utilization and aerobic oxidation rate, a drop in biomass yield, prolongation of cultivation time, etc. The inhibitory effect of crotonaldehyde depends strongly on the manner of its dosage into the medium (single or continuous) and other cultivation conditions (intensity of medium aeration, physiological state of the culture, etc). Crotonaldehyde is lost from the medium partially by volatilization and partially due to chemical and biochemical transformation.


Predactious fungi Dactylaria pyriformis and Dactylaria thaumasia: production of attractants and nematicides. Dactylaria pyriformis Juniper and Dactylaria thaumasia Drechsler are predacious fung forming three-edimensional sticky reticula in which nematodes are captured. It was shown by methods developed in our laboratory that in submerged cultivations both of these fungi produce substances attracting nematodes and compounds having nematicidal activity.


[Germinal testicular tumors].

[Germinal testicular tumors]. Characteristic for the germinal cell tumors of the testis is their great variety. Collins and Pugh gave a classification of testis tumors under consideration of the genesis of the tumor and the clinical progressing. The staging should be done according to the TNM-system which is based on the UICC recommendations of 1973. If a tumor is suspected an exploration of the testis must be performed. After definitive histological diagnosis via immediate section for microscopic examination during surgery an enlarged orchiectomy and local lymph node dissection has to be performed. In cases of seminoma a 5-year-survival-rate of 90 to 97 per cent can be achieved by radiation of two fields (4 fields in case metastases are suspected). Because of the radio resistance of the teratoid tumors a retroperitoneal lymph node dissection has to follow the enlarged orchiectomy. With a subtile operating technique all the lymph nodes between diaphragm and aortic bifuraction can be removed in case of operability. Postoperative radiation therapy is only recommended in case of excessive lymph node metastases. By an adjuvant chemotherapy following retroperitoneal lymph node dissection a 5-year-survival-rate of more than 80 per cent can be obtained in cases of teratoid tumors.


[Morpholgical changes in the rabbit's bladder after argon laser irradiation]. After developing a flexible fiber light guide and a special cystoscope it was possible to study the Argon laser beam effects on the bladder wall of rabbits and dogs. It could be proved that the Argon laser is qualified for the use in organs with thin walls, especially in the urinary bladder, because of its strong absorption in tissue with high blood flow and its minor penetretion depth. However, our further investigations showed--they shall be published--that the output of the Argon laser used in our studies not sufficient for destroying human bladder tumors. For this reason it is necessary to use neodymium YAG laser.


[Synthesis and biological activity of the decapeptide Gly-Pro-Cys-Lys-Ala-Arg-Phe-Gly-Gly-Cys as a model for the active center of the basic trypsin inhibitor from bovine organs (Kunitz inhibitor) (author's transl)]. The synthesis of the above mentioned decapeptide as a model for the active center of the inhibitor molecule is described. The Ki value of this peptide was found to be 4.7 X 10(-4)M. This Ki value differs from the Ki value of the Kunitz Inhibitor by a factor of 10(10).