[Normal excretion of corticosteroid hormones in rat urine studied by a thin-layer chromatographic method]. The author examined the parameters of normal excretion of cortico steroid hormones and their metabolites in urine of rats (11 single fractions) by the method of a thin-layer chromatography. The data could be accepted as norms of corticosteroid excretion in urine of young adult rats of the strain Wistar. Nine biological important indices e-corticosteroids in urine of normal rats were described. He discussed the physiological pecofliarities of the normal excretion of corticosteroid hormones and genetical and/or nongenutical factors, determining corticosteroid formula in urine of the rat. He indicated the significance of a thin-layer chromatography for the determination of corticosteroid excretioi-for the evaluation of the functional state of the adrenal cortex and liver under various experimental conditions.


Seizure disorders in offspring of parents with a history of seizures - a maternal-paternal difference? If the patterns of seizure disorders in parents and offspring could be assessed accurately, some insight might be gained into the relative role of genetic and environmental factors in the development of convulsive disorders. In this study 908 children born in a Rochester, Minnesota hospital from 1922 through 1972 whose mother or father had a verified and classified diagnosis of seizure have been followed from birth for evidence of any convulsive episode or seizure disorder. The observed numbers of various types of convulsions in the offspring are compared to the expected the number based on local age-specific incidence rates. The outstanding finding was that a higher than expected number of children whose mothers had epilepsy also suffered from seizures (epilepsy or febrile convulsions), whereas no such increase was detected among the children of affected fathers.


Neuropsychological correlates of the electroencephalogram in epileptics: II. The waking posterior rhythm and its interaction with epileptiform activity. Relationships between psychological functions and waking dominant posterior rhythm frequency (DPRF) of the EEG were evaluated with and without simultaneous evaluation of epileptiform discharges. Ninety adult epileptics with uncontrolled seizure disorders treated solely by diphenylhydantoin underwent EEGs during wakefulness and administrations of an extensive battery of neuropsychological tests. The DPRF was particularly related to abilities simultaneously requiring attention an complex mental manipulations. Rhythms slower than 7.5-8.0 Hz were accompanied by relatively poorer performance than rhythms which were faster. When epileptiform discharges were considered in combination with the DPRF, larger differences in abilities were demonstrated, and the psycholoigcal correlates tended to be more substantial for the epileptiform discharge variable than for the DPRF variable. The selection of tests employed and the range of rhythms assessed are critical to these findings, and the substantial construction of these variables by many previous investigators is believed to be related to the negative findings often reported.


Ischemic heart disease in patients with epilepsy. It has been suggested that patients with epilepsy and particularly those on long-term anticonvulsant medication may have a lower than expected risk of ischemic heart disease. The records of a cohort of patients with epilepsy in Rochester, Minnesota were reviewed to ascertain their rates of occurrence of ischemic heart disease. The results did not show any relative decrease in the incidence or mortality rates due to ischemic heart disease among men or women with epilepsy. The numbers of ischemic heart disease incidence and mortality cases were 25 and 15, respectively, relative to corresponding expected values of 15.0 and 15.7 new and fatal events. The use of anticonvulsant medications did not appear to influence the rates of ischemic heart disease among the patients with epilepsy. Subgroups of the epilepsy patients, by etiology and types of epilepsy, were not found to account for a disproportionate share of the ischemic heart disease. The survivorship of epilepsy patients after the initial manifestations of ischemic heart disease was comparable to that expected among all ischemic heart disease patients.


Ketamine hydrochloride and its effect on a chronic cobalt epileptic cortical focus. The effects of anesthetic and nonanesthetic doses of ketamine hydrochloride were studied in male adult rats in which a primary and a projected epileptic focus were induced with implantation of cobalt in the right or left frontal cortex. Electrical activity was recorded from the frontal, parietal, and occipital cortices. Nonanesthetic doses of ketamine were associated with activation or enhancement of primary and projected focal electrical activity, as well as turning behavior toward the side of the cobalt focus. Anesthetic doses of ketamine also enhanced or activated the primary and projected foci. These animals demonstrated turning behavior toward the side of the cobalt focus prior to and following the cataleptoid state. During catalepsy, forelimb twitching and oscillating movements of the vibrissae occurred. The activation of primary and projected foci by ketamine at anesthetic and nonanesthetic doses supports the clinical findings that ketamine is epileptogenic in certain patients with a seizure disorder.


Convulsive fits in thyrotoxicosis.

Convulsive fits in thyrotoxicosis. A patient with hyperthyroidism is described who developed grand mal seizures when anth-thyroid medication was withdrawn. Pyramidal signs were also present. The EEG reverted to normal and the clinical signs and symptoms disappeared when his thyroid status was again controlled.


Serum concentration of carbamazepine: comparison of Herrmann's spectrophotometric method and a new GLC method for the determination of carbamazepine. A specific direct gas chromatographic method to determine carbamazepine and, semiquantitatively, 10,11-epoxy carbamazepine in serum is described. The average recovery of carbamazepine is 98%, and the error on duplicate determination is +/- 4%. The method is compared with Herrmann's classic spectrophotometric method. In material of 103 patients the mean serum concentration of carbamazepine was 25.5 +/- 12.8 mumoles/1 with GLC and 23.0 +/- 12.6 mumoles/1 with spectrophotometry. The difference was highly significant. The blood sample volume is one-tenth of that needed in spectrophotometry.


Changes in biochemical and physiological indices in animals produced by the combined effect of benz [a] pyrene and phenol. Early energy changes in lungs, liver, and kidneys during the introduction of a benz a pyrene and phenol (as the possible carcinogen activator) were studied. It was observed that 10 days after a single instance introduction of 5 mg benz a pyrene per 0.9% NaCl (60 rats), oxidative phosphorylation in the lungs and livers is disturbed in the test rats, accompanied by a reduction of adenine nucleotides in these tissues. It is assumed that at this stage, the detoxication of benz a pyrene is intensified by free oxidation systems and by the respiratory chain of mitochondria. A chronic 3-month exposure to benz a pyrene and phenol (150 rats, each 5 mg of benz a pyrene per month intratracheally and 0.4 mg/m3 of phenol round-the-clock) results in greater disturbances of the energy exchange in the lungs, liver and kidneys. Benz a pyrene and phenol, individually and in combination, inhibit oxidative phosphorylation in the lungs. This significantly decreases the content of adenine nucleotides in this tissue. Activation of anaerobic glycolysis (twofold) and of aerobic glycolysis (eightfold) does not make up for the energy insufficiency in the tissue. The effect of benz a pyrene and phenol in the liver also results in suppressing oxidative phosphorylation and in the activation of glycolysis (anaerobic 2.5 times, the aerobic 3.7 times). Changes in the bioenergy of the kidneys are not as great. Phenol in its combined effect with benz[a]pyrene intensifies the effect of the latter, as shown primarily to the greater activation of anaerobic and aerobic glycolysis in the lungs and livers of test rats. The observed disturbances as concern the weight dynamics of the animals (weight loss in test rats), vitamin metabolism (their decrease in the organs in in urine) and hemopoiesis of red blood cells (erythropenia) attest to the toxic effect of benz a pyrene phenol on the organism, which is greater in the case of the combined action of the studied agents. No changes were discerned in the morphology of white blood cells.


Combined exposure to ozone and nitrogen dioxide. The combined effects of ozone and nitrogen dioxide were assessed in an in vitro test system utilizing human red cells. In general, these two pollutants had additive effects on the parameters measured which included osmotic fragility, acetylcholinesterase activity, lipid peroxidation, reduced glutathione and methemoglobin levels. However, at lower pollutant doses a synergistic increase in lipid peroxides was noted while at higher doses the effect became less than additive. Further studies of this observation suggested that ferrous hemoglobin potentiates ozone-induced lipid peroxidation while methemoglobin, resulting primarily from nitrogen dioxide, inhibits this process. Ozone was also found to potentiate the methemoglobinemic effects of nitrogen dioxide, particularly in sequential studies in which ozone exposure preceded nitrogen dioxide. Inasmuch as the effects of these two pollutants vary from protective to synergistic depending on the pollutant concentration, duration and sequence of exposure, as well as on the parameter assayed, it would appear that the approach to in vivo study of the combined effects of ozone and nitrogen dioxide should be aimed at simulating ambient conditions as closely as possible.


Time--dose response for nitrogen dioxide exposure in an infectivity model system. The concentration of NO2 in polluted atmosphere is subject to wide variation, according to peak traffic load, industrial productivity, intensity of sunlight and meteorological conditions. Normally NO2 has a low basal concentration with superimposed spikes when the above conditions are optimal for its production. Thus, it is important to determine the relative importance of a short-term, relatively high concentration of NO2 versus exposure for longer periods of minimal dose levels. This problem was approached experimentally by measuring the effect of NO2 on an animal's resistance to the induction of bacterial pneumonia. The data collected indicate that: (1) in short-term dose-response studies using the same Ct (concentration x time) product of 7, the actual concentration exerts a greater influence on NO2 effect than does the duration of exposure; (2) when concentration is held constant and the time increased, the average difference in mortality from controls can be seen after only 1 hr exposure to 3.5 ppm and after 3 weeks of exposure to 0.5 ppm; and (3) the relative mean survival time at 3.5 ppm for 1 hr was 18--36 hr less than that of the control animals.


Methodological approaches to the study of the combined effect of atmospheric pollutants as illustrated by chlorinated hydrocarbons. The combined effect of substances with a unidirectional toxic action was studied with the use of several chlorinated hydrocarbons, including 1,2-dichloropropane, 1,2,3-trichloropropane, and perchlorethylene at various concentrations. The results of the study can be used as the basis for the development of methodological approaches to the study of the combined action of toxic substances administered by inhalation. The research plan also incorporated the problem of explaining the nature of the action of the mixture of the test compounds in acute, subacute, and chronic animal experiments. All of the studies were conducted with each compound alone and then in various combinations by using the concentration--time relationship, since a correct evaluation of the combined action of compounds can be obtained by comparing these with the effects observed for the action of each component alone. A graphic representation was obtained of the onset time for a given effect (loss of righting reflex for 50% of the animals) as a function of the active concentrations for the short-term effect of high concentrations of 1,2-dichloropropane, 1,2,3-trichloropropane, and perchloroethylene based on the concentration--time relationship. The nature of the combined action of various combinations (two and three substances) with respect to concentration was studied by using these graphs. At high concentrations, the action of various combinations of the studied substances is additive. An inverse relationship was discovered in subacute experiments between the inactive concentrations and the onset time for changes in the vital activity indices of an organism: the lower the concentration, the later the changes. Additional data were obtained as the result of morphofunctional studies on the toxic properties of the studied compounds, on damage reactions and on adaptational changes. This is of interest from the point of view of explaining the mechanism of action at various concentrations.


Effects of toxaphene on hepatic enzyme induction and circulating steroid levels in the rat. Rats were given a single dose of toxaphene (120 mg/kg, equivalent to 1/2 LD50) and sacrificed at 1, 5, and 15 days. Liver weight and hepatic microsomal enzyme activity were increased at day 5 and 15. The level of plasma testosterone was significantly decreased at day 15. In a second experiment rats were given 2.4 mg/kg daily and sacrificed at 1, 3 and 6 months. Liver weight and microsomal enzyme activity were significantly increased over controls; enzyme activity was, however, decreasing by the end of the experiment. Plasma testosterone levels were not affected. It is concluded that enhanced hepatic enzyme induction causes only a transient drop in circulating testosterone levels followed by a return to normal values.


Experimental study of the effect of a series of phosphoroorganic pesticides (Dipterex and Imidan) on embryogenesis. Experiments conducted on pregnant Wistar rats show that chlorophos (Dipterex) has embroyotoxic and teratogenic effects after oral introduction in a 80 mg/kg dose during a critical period of embryogenesis. Embryotoxic and teratogenic effects are absent during the introduction of 8 mg/kg of the pesticide. The oral introduction of phthalophos (Imidan) in a 30 mg/kg dose once on day 9 of pregnancy and the introduction of a 1.5 mg/kg dose daily throughout the course of pregnancy caused increased postimplantation mortality of embryos. A dose of 30 mg/kg of phthalophos on day 9 or day 13 of pregnancy causes developmental abnormalities, including hyponathia and hydrocephaly. A 0.06 mg/kg phthalophos dose does not affect the course of embryogenesis in white rats. Thus the organophosphate pesticides Dipterex and Imidan exhibit embryotoxic and teratogenic effects at doses which significantly exceed the acutal amounts of the pesticide that can enter the human organism.


Effect of chlorocamphene on the isoenzyme spectrum of lactate dehydrogenase in rat serum and liver. Rats were used to study the general activity and the isoenzyme spectrum of lactate dehydrogenase (LDH) during single-instance and long-term introduction of polychlorocamphene. Total lactate dehydrogenase activity decreases in the liver during the single-instance introduction of half the LD50 (120 mg/kg). The isoenzyme spectrum of LDH is characterized by an increase in the quantity of LDH1, LDH2, and LDH3 and by a decrease in the amount of LDH4. The overall LDH activity does not change in blood serum. The isoform ratio changes insignificantly and LDH1 falls, but normalized 15 days after the introduction of the compound. Long-term introduction of polychlorocamphene at levels 1/100 the LD50 dose over 1.3 and 6 months causes a reduction in the overall LDH activity, both in the liver and in the serum. A decrease in the activity of the basic LDH isoenzyme of the liver (LDH5) and a sharp increase in LDH3 are characteristic for the isoenzyme spectrum of the liver. LDH1 and LDH4 decrease and LDH2 and LDH3 increase in blood serum. Beginning with the third month of polychlorocamphene introduction, LDH1 tends to return to normal levels. LDH2, LDH3, and LDH4 do return to normal levels, while LDH5 increases regularly. This results in a reduction of the number of H subunits and an increase of M subunits. This is characteristic of hypoxic states. On comparing the changes in the LDH enzymes of the liver and blood serum, it can be considered that the introduction of polychlorocamphene does not result in an increase in the permeability of the cellular membranes of the liver for LDH isoenzymes, while the observed isoenzyme spectrum shifts in blood serum are either the result of the biosynthesis of the isoforms of this enzyme changed by the compound or the result of the permeability for them of cells of other tissues.


Methods for detecting teratogenic agents in man. At a multidiscipline international meeting sponsored by L'Institut de la Vie held at Guadeloupe in January 1974, current methods for detecting teratogenic agents were outlined and discussed. Recommendations of the participants of the conference were: recognize the limitations of the present defenses against teratogenic agents; educate the public and medical profession about the known human teratogenic agents; select for animal teratogenicity screening among new and existing agents by emphasizing substances to which the entire population will be exposed, agents to which pregnant women are exposed, viruses which are found to persist in the human fetus, and agents which have become suspect from clinical experience; recognize that nearly all compounds have a fetotoxic dose but that this does not imply teratogenicity; encourage the development of new, quick in vitro testing methods for detecting teratogenic agents; monitor for sudden increases in the frequency of specific malformations in newborn infants and in aborted fetuses; assure that expert multidiscipline committees are available to evaluate the threat when suspected teratogens are reported; improve teratology information storage and retrieval systems by record linkage of clinical data, linkage between computer systems, and universal identifier system for chemical compounds and congenical malformations; foster the exchange of data, particularly those held by the pharmaceutical industry.


Concentration--time relationship for various regimens of inhalation of organic compounds. An attempt was made to establish a concentration--time relationship for continuous and interrupted inhalation of a number of nonelectrolytes to establish norms for the permissible content of harmful substances in atmospheric air. The tests showed that the indicated relationship can be expressed in the form of a straight line on a logarithmic grid by using either acute toxicity parameters or the onset of physiological and biochemical shifts. This makes it possible to predict the chronic effect thresholds of substances on the basis of the results of short-term experiments.


Chemical structure and properties of selected benzene compounds in relation to biological activity. Four fundamental physical parameters of series of benzene derivatives were studied to ascertain correlations with biological activity. These included octanol/water coefficient, vapor pressure, infrared absorption (out-of-plane C-H vibration), and the pi values. Each physicochemical constant exhibited a partial correlation with biological activity suggesting that each played a role. It was presumed that more precise and specific data on the biological activity would have permitted a better correlation. It is postulated that the biological activity of a compound is due to the sum of such physicochemical factors as: partition coefficient, molecular geometry and spatial orientation, electronic characteristics of the molecular orbitals, and vibrational-rotational frequencies of constituent groups.


Predicting biological effect as a function of the chemical structure and the primary physical and chemical properties of organic compounds. The dependence of biological parameters on chemical structure was studied for a series of compounds with similar chemical structures. Computational formulas were developed on the basis of correlation and regression analysis. These formulas make it possible to predict the biological effect thresholds for a great number of organic compounds on the basis of their primary physical and chemical properties.


Studies in the behavioral toxicology of environmental contaminants. Behavioral toxicology represents a relatively new research area in the West, and a new source of information pertinent to standard setting. Despite this abbreviated history, however, it can call on a rather advanced technology, largely provided by the rapid and extensive development of behavioral pharmacology during the past two decades. As exemplified by the U.S. contribution to the joint study of carbon disulfide, the approach derived from this background relies on the acquisition of dose--effect data with a preparation yielding stable baseline performance. The first study in this collaborative series employed pigeons trained to peck a response device consisting of a transilluminnated plastic disk. Various relationships between this response and the occasions on which it led to the delivery of food were explored in order to ascertain which behavioral variables were most sensitive to acute exposures. In addition, a central nervous system drug, whose neurochemical mode of action is believed to parallel that of carbon disulfide, was tested in the same preparations. Further research on these questions is being continued with monkeys.


Investigation of the mechanism of action of atmospheric pollutants on the central nervous system and comparative evaluation of methods of study. Some aspects of the mechanism of action of atmospheric pollutants (acetone, benzene, ammonia, formaldehyde, and ozone) on the central nervous system were studied by using methods of functional electroencephalography (analysis of the readjustment reaction to a rhythmic light stimulus, evoked potentials of the cerebral cortex, and determination of the photometrazol thresholds). Effects of the compounds were determined for the various structures of the cerebral cortex of experimental animals. The most sensitive structures were those which were first to associate in the reaction to toxic agents (the corticomedial nucleus of the amygdaloid complex and the olfactory bulb). EEG indices were observed which were indicative of an adverse effect (epileptoid activity in the most sensitive formations of the brain and a stable generalized stress rhythm in the neocortex and in the limbic ascending reticular system). During long-term action of toxic materials at low concentrations, changes were observed in the parameters of the primary and secondary responses of the visual evoked potential which were indicative of a disturbance of the cortical inhibition processes. This can be considered one effect of atmospheric pollutants at low concentrations. Problems of the comparative sensitivity of the various methods of studying the central nervous system are being investigated with a single compound: carbon bisulfide. In human experiments concerned with the fine coordination of measured movements such as writing and the solution of arithmetic problems, the subject-operator observed that repeated inhalation of subsensory concentrations of carbon bisulfide (0.08 mg/m3 level) disturbs the rate of execution of assigned motor processes. In tests with rats with developed instrument conditioned reflexes, it was shown that entire behavioral acts deteriorate under the effect of the same carbon bisulfide concentration. In tests on rabbits, simultaneous neurophysiological and neurochemical analyses were performed on the changes in the functional state of the central nervous system under chronic exposure to carbon bisulfide at various concentrations.


Methods to assess reproductive effects of environmental chemicals: studies of cadmium and boron administered orally. Results of a U.S.S.R.--U.S. cooperative laboratory effort to improve and validate experimental techniques used to assess subtle reproductive effects in male laboratory animals are reported. The present studies attempted to evaluate the reproductive toxicity of cadmium as cadmium chloride and boron as borax (Na2B4O7) and to investigate the mechanism of toxicity in the rat following acute and subchronic oral exposure. In vitro cell separation techniques, in vivo serial mating tests, and plasma assays for hormones were utilized. Effects on the seminal vesicle and prostate were evaluated with chemical and enzyme assays. Clinical chemistry was monitored routinely. Acute oral doses, expressed as boron were 45, 150, and 450 mg/kg while doses for cadmium equivalent were 6.25, 12.5, and 25 mg/kg. Rats were also allowed free access to drinking water containing either boron (0.3, 1.0, and 6.0 mg/l.) or cadmium (0.001, and 0.l mg/l.) for 90 days. Randomly selected animals were studied following 30, 60, and 90 days of treatment. These initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity.


Toxic and gonadotropic effects of cadmium and boron relative to standards for these substances in drinking water. Experimental research was conducted on the study of the relationship of the general toxic and gonadotoxic effects of cadmium and boron under conditions of subacute and chronic oral intoxication on white random-bred rats, by use of biochemical, physiological, cytological, and pathomorphological methods. It is shown that the gonadotoxic effect of cadmium is manifested on the same level (3 mg/kg of body weight) as the general toxic effect. The gonadotoxic effect of boron is dominant and is manifested at a lower level (6 mg/kg of body weight) than the general toxic effect (20 mg/kg). On the basis of the results of chronic experiments, 0.001 mg/l. is recommended as the hygienic standard for cadmium in water and 0.5 mg/l. for boron.


Physicochemical properties of some organophosphates in relation to their chronic toxicity. Organophosphates in increasing amounts and wider varieties of molecular structure are being used to replace the organochlorine pesticides. It has been assumed that the organophosphates as a class would have a minimal chronic toxicity due to rapid hydrolysis and an unfavorable partitioning as regards to lipids. The physicochemical properties of a number of representative organophosphates were determined, including the octanol/water partition coeffecient, hydrolysis, and binding to proteins. Those having a halogenated aryl substitution were found to have partition coefficients not largely different from the organochlorines, suggesting the possibility of fat deposition. Certain of these compounds are sufficiently stable toward hydrolysis to allow bioaccumulation to occur. These preliminary findings appear to indicate a correlation between readily determined physical properties and the potential for chronic effects in this class of compounds.


Methods for predicting chronic toxicity parameters of substances in the area of water hygiene. The development of rapid methods for determining chronic toxicity parameters of chemical compounds introduced by the oral route into an organism with water was studied. Formulas are verified with which threshold values and no-effect toxicity doses for substances can be obtained on the basis of various toxicologic parameters. For the example of organophosphates, a methodological scheme was developed for conducting an accelerated experiment for predicting the chronic toxicity of low and average cumulative compounds. Results are presented indicating the inadvisability of using lower animals as test subjects with the aim of predicting toxicity for higher animals. It is pointed out that patterns of homology and isomerism are observed in the comparison of chronic intoxication threshold doses as well as in acute toxicity values of substances.


Assessment of environmental carcinogen risks in terms of life shortening. An approach is presented to the assessment of carcinogen risks in which the dominant effect of carcinogen exposure is life shortening and the impact falls both on those individuals who would have gotten cancer without the carcinogen exposure as well as the new cancer cases. This analysis is based on the interaction of age-specific tumor incidence rates and population survival in terms of age-specific mortality rates without the induced risk from carcinogen exposure. The analysis yields estimates for lifetime probability of developing cancer, average lifespan lost by the entire population, the average age of cancer occurrence, and the average lifespan loss of cancer cases. The approach utilizes the animal response data to assign, to the existing human cancer occurrence, and equivalent dose of the same carcinogen which is under consideration in terms of risk evaluation. The approach has the advantages of keying the estimates of carcinogen risks to those which already exist in the environment, advoiding large extrapolations from animal data, and encompassing the variability in susceptibility and carcinogen exposure in humans.


Predicting the risk of tumor occurrence under the effect of small doses of carcinogens. Basic methodological approaches were formulated for determining the permissible levels of carcinogens in man's environment on the basis of current experimental oncological data dealing with the interaction of the organism and carcinogenic compounds. The tumor is proposed as a specific index of the harmfulness criterion of carcinogenic action. Under these conditions, both the frequency and the development time of tumors must be considered. Results are given of an experimental study of the carcinogenic activity of various doses of benz[a]pyrene (0.005, 0.02, 0.1, 0.5, and 2.5 mg) on rats by using a tenfold intratracheal administration. On the basis of mathematical models of the obtained dose-time-effect relationship, the risk of cancer occurrence due to small carcinogen doses is predicted. Small doses were not tested in the experiment. On the basis of the data obtained in the experiment, a maximally permissible concentration of benz a pyrene in the ambient air can be determined. A benz[a]pyrene dose of 0.02 mg is recommended as the basis of the calculation. The effect of this dose is shown at time periods longer than the limits of human life.


[Studies on the value of fecal tryptic and chymotryptic activity in the diagnosis and therapy of cystic fibrosis (author's transl)]. Under certain conditions the determination of the tryptic activity, especially of the chymotryptic activity in the feces mostly of infants in the first 4-6 weeks of life is considered to be an important step in the diagnosis of cystic fibrosis. The tryptic anc chymotryptic activity in the feces of children with cystic fibrosis declines when the substitution of pancreatic enzymes is stopped. On resubstitution, the activity rises in relation to the dose and attains the activity related to age as found in healthy children. A comparison of the proteolytic activity with the fat content of the feces during the study period without the enzyme substitution and during the period when the enzyme dosage varied showed no significant correlation. It is not possible to postulate a poor excretion of fats merely from the high proteolytic activity of the feces because the fecal proteolytic activity and the fat excretion are not inversely proportional to one another. For this reason, one cannot conclude that the grade of the proteolytic activity in the feces of patients with cystic fibrosis is a yardstick for the total digestive process when they are under pancreatic enzyme substitution.


Malignant disease of infancy and childhood with special reference to leukaemia: a survey of 6431 autopsy cases. A study on the prevalence of cancer at autopsy in Chilean children with special reference to leukaemia, was made. In a series of 15300 consecutive autopsies of Chileans, 70% of deceased patients had an autopsy. Of these 15300 cases (male:female ratio 1:0.92) 6431 were children (0-15 years of age); 90% of deceased children patients had an autopsy. The autopsy population of children and adults is a homogeneous ethnic group, and exhibits a low socioeconomic level. Data on the 6431 post-mortem examinations (1945-1966) came from the atuopsy records of five hospitals (four of them are teaching hospitals) in the city of Santiago. Each one of the leukaemia and solid tumour cases were diagnosed microscopically. In the children population, 54.92% were males and 45.08% were females. Of the 6431 autopsies, 142 exhibited cancer (2.21%), 2.43% being male cases and 1.93% being female cases. The autopsy cases showed a marked excess of boys (73.92%) and girls (69.77%) under 1 year of age. The prevalence of major morphological groups of cancer was as follows: leukaemias 50.70%, intracranial and other neural neoplasms 25.35%, malignant lymphomas, including Hodgkin's disease, 14.07%, and mixed malignant tumours (Wilms' tumour) 4.93%. 4.93%. Acute leukaemias (42.96%), medulloblastoma (7.65%), Hodgkin's disease (6.34%), Wilms' tumour (4.93%), and lymphosarcoma (4.93%) were the most prevalent types of cancer. Leukaemia cases had a corrected male:female ratio of 1:0.61. The prevalence of leukaemia in the atuopsy population was 1.12%.


Hemoglobin chain synthesis in two children with trisomy 13. Evidence for temporary imbalance during switch from gamma to beta chain synthesis. Hemoglobin chain synthesis was studied in 2 infants with trisomy 13, one in the newborn period, the other at 5 months of age. The relative rate of beta globin synthesis was much below normal in the newborn, resulting in an overall imbalance of nonalpha/alpha globin synthesis. In the 5-month-old child, globin synthesis was balanced, although gamma globin synthesis accounted for a larger than normal percentage of nonalpha globin synthesis. Thus, the presence of a third 13 chromosome causes sever disturbances in the gamma to beta switch mechanism primarily affecting the onset of beta globin synthesis. The appearance of two previously unobserved bands in isoelectric focusing gels of the newborn's Hb is suggestive of the presence of embryonic hemoglobins.


Mean 24-hour growth hormone and testosterone concentrations in relation to pubertal growth spurt in boys with normal or delayed puberty. The mean growth hormone concentration during 24-hour period in 7 boys of short familial stature and a growth rate of 3.2-5.4 cm/year was between 1.0 and 4.6 ng/ml serum. In 7 boys with pubertal growth spurt and familial tallness (growth rate 7.2-11.0 cm/year) it varied from 0.97 to 4.4 ng/ml and in 6 boys with constitutional delay of puberty (a growth rate of 4.2-5.2 cm/year prior to puberty) from 1.3 to 4.3 ng/ml. No correlation was found between the 24-hour mean growth hormone concentration and the mean 24-hour testosterone concentration in serum or the growth rate, but a correlation was found between testosterone and the growth rate. It is concluded that the growth spurt in puberty is not due to a change in growth hormone concentration but rather to the increase of androgen production in puberty.


The problem of toxicity in the bioassay for erythropoietin using mouse fetal liver cells. The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity. Heating the Step I or Step III sheep plasma erythropoietin had very little influence. Fetal calf serum proved to be more suitable than neonatal calf serum for two reasons: The toxicity of human sera was less pronounced when fetal calf serum was used in the medium, and it gave a wider separation of unstimulated and maximally stimulated cultures.


Effect of Rauscher leukemia development on DNA synthesis by hematopoietic CFU-S. The effect of Rauscher viral leukemia on the number of colony forming cells (CFU-S) in the spleen has been measured as a function of time after virus administration. These were increased substantially after the first week, reaching a maximum at 2 weeks, after which they decreased in number. Determination of the proportion of these CFU-S which were in DNA synthesis was carried out using the in vitro 3HTdR suicide technique. Within 4 hours of injection of the virus the number of spleen CFU-S which could be inactivated by in vitro 3HTdR exposure increased to 20.9% from a normal mean value of 10.2%. For the next 2 weeks the proportion of CFU-S responding to tritiated thymidine exposure remained at the same value of approximately 20%; the change in number of surviving CFU-S roughly paralleled the change in total colony forming cells. In the third week after virus injection, the proportion of CFU-S which was inactivated by 3HTdR decreased to the point where it could no longer be detected, even though the total number of CFU-S was elevated several fold over the normal. These findings indicate that infection with moderate dose levels of Rauscher virus does result in a measurable early increase in the proportion of cells in DNA synthesis. However, the failure to detect further substantial increases as the disease develops suggests that the virus of itself is not an initiator of all the steps of DNA synthesis. Rather, it would appear that it is to some degree dependent upon other aspects of normal DNA synthesis which remain under control of the cell.


Effect of serum from leukapheresed mice on myelocytes, promyelocytes and colony-forming cells. Leukapheresis of neutrophil granulocytes in mice increased the myelopoietic activity of their serum. Leukapheresed mouse serum (LMS) caused a threefold increase in the in vitro stathmokinetic index of myeloid precursors. Five to ten minutes of incubation were sufficient to change the colony-forming capacity of mouse bone marrow cells as expressed by the increase in the ratio of granuloid to erythroid cells in spleen colonies. The in vitro stathmokinetic index assay also showed that there are diurnal variations in levels of granulopoietic activity in normal mouse sera. However, at any time of the day, LMS had higher granulopoietic activity.


Correlation between splenic phagocytic activity and increase in splenic granulocyte/macrophage progenitors. The possible connection between changes in splenic phagocytic activity and increase of splenic macrophage/granulocyte progenitors (colony forming cells - CFC) in mice was studied. Intravenous administration of increasing amounts of colloidal carbon, or sheep red blood cells (SRBC), 3 hours prior to injection of 10(7) 51Cr labeled SRBC caused a decrease in phagocytic activity in liver and an increase in spleen. Under the same experimental conditions, injection 10(7) unlabeled SRBC induced an increase of splenic CFC. Increase in splenic phagocytic activity and in numbers of splenic CFC showed a linear relationship. Both activities depended on the amounts of colloidal carbon or SRBC injected prior to injection of 10(7) SRBC. These findings suggest that mature macrophages may participate in controlling the increase in number of splenic CFC after injection of particulate substances such as SRBC or colloidal carbon. It was also found that increase of splenic CFC, under the experimental conditions described, was not affected by neonatal thymectomy.


Thymic influence of proliferation and interaction of fractionated spleen cells of mice. Cells from the spleens of mice were separated into seven subpopulations by centrifugation on a discontinuous density gradient of dextran. The lightest fraction (containing stem cells), the three heaviest fractions (containing small lymphocytes), or a mixture of these, were injected into thymectomized or sham-thymectomized irradiated mice together with sheep red blood cells as antigen. After 8 days, the spleens of treated mice were tested for their content of cells lysing sheep red blood cells in agar (PFC) or cells mounting graft-versus-host reaction in newborn mice (GVHR). Heavy fractions were depleted of progenitors of PFC, but contained progenitors of cells mounting GVHR. The light fraction was depleted of both. If light cells were given together with heavy ones, the potential to generate PFC was restored, but only if the recipients were without their thymus; by contrast, the potential to generate GVH-reactive cells was strongly suppressed in the absence of a thymus. It is concluded that, in this model, stem cells probably interact with immunocompetent cells, and that the interaction depends on the thymus.


Evoked cerebral responses to noxious thermal stimuli in humans. Brief pulses of Laser emitted radiant heat were used to induce cutaneous painful sensations in human volunteers. Accurate timing of the stimuli permitted recording of scalp averaged evoked potentials. A late negative-positive component of the EP which correlated in amplitude with the subjective sensation was observed in four subjects. The latency of this component (130-160 msec) correlated with stimulus intensity.


Behavioural compensation of cats after early rotation of one eye. Two cats, each with one eye surgically rotated by about 90, were trained (by two different behavioural methods) to discriminate horizontal from vertical stripes using the normal eye alone. When they had mastered the discrimination, the normal eye was occluded and the rotated eye was tested for transfer with neither stimulus reinforced. Both cats responded immediately and consistently to the same stimulus that they had learned to choose with the normal eye. These animals seem to have adapted to eye-rotation not only in terms of spatial localization but also in terms of the recognition of the orientation of contours. These behavioural compensations cannot be accounted for by simple changes in the organization of the visual cortex.


Effect of oxotremorine on the response of antidromically activated Renshaw cells in decerebrate cats. In intercollicular decerebrate cats, some of which were made spinal in addition, the effect of oxotremorine (intravenous injection, 10-30 mug/kg) was tested on antidromically activated Renshaw cells. Methylatropine premedication prevented the otherwise often fatal drop in blood pressure; ipsilateral dorsal roots L6-S1 and contralateral hindlimb nerves were cut to exclude segmental receptor interference. During supramaximal stimulation of ventral root L7 or the gastrocnemius nerves, an increase of activity ranging from 10-110% was observed. The drug occasionally evoked spontaneous discharges in Renshaw cells, or enhanced activity already present. Alpha motoneuron activity decreased in most cases. The interaction of oxotremorine with atropine and eserine was also investigated on Renshaw cells. Our results suggest that one of the effects of oxotremorine may be a disbalance between motor output and recurrent inhibition.


Characteristics of single mechanoreceptive fibres innervating hairy skin of the human hand. Unit activity was recorded percutaneously by microelectrodes from 69 nerve fibres innervating the hairy skin of the back of the hand in 6 awake human subjects. Twelve fibres had no receptive field on the skin, twenty-one fibres could be classified as rapidly adapting (RA) and thiry-six fibres as slowly adapting (SA) mechanoreceptive fibres. Four SA fibres has a spontaneous discharge in absence of stimulation. Mechanical thresholds of tra fibres ranged from 0.3 to 1.7 g and those of SA fibres from less than 0.1 to 1.7 g. Conduction velocities of the fibres were 22-41 m/s (RA fibres) and 10-73 m/s (SA fibres). Intensity functions of SA fibres could be described by power functions with exponents varying between 0.31-1.23. Most RA and SA fibres were entrained by vibratory stimuli. The results indicate that the receptors in the human hairy skin do not differ considerably in their characteristics from the receptors in the human glabrous skin or from animal receptors in the hairy skin.


Properties of LGN cells in kittens reared with convergent squint: a neurophysiological demonstration of amblyopia. The spatial resolution of LGN cells has been studied in 4-5 month old kittens raised with convergent squint surgically produced in one eye at the age of 3-4 weeks. The 'sustained' cells which received inputs from the central retina of the squint eye showed significantly poorer spatial resolution (determined by the highest spatial frequency of a sinusoidal grating to which a cell responded with modulated firing) than those which received inputs from the central retina of the normal eye. The spatial resolution of cells which received inputs from the peripheral retina of the squint eye was not different from that of cells receiving inputs from the peripheral retina of the normal eye. The visual latency of 'sustained' cells which received an input from the area centralis of the squint eye was considerably lenghtned and the response showed a sluggish onset. Thus the most important clinical symptom of amblyopia, namely the reduction of foveal visual acuity, has been demonstrated in kittens raised with unilateral vonvergent squint. The results suggest that the lesion responsible for amblyopia due to squint might be a functional degeneration of the high spatial frequency tuning cells in the pathway prior to the visual cortex, i.e. in the retina or LGN.


14-3-2 protein in rat primary and transplanted gliomas and neurinomas and in clonal cell lines. Experimental neurogenic tumors were induced transplacentally in rats by single injections of ethylnitrosourea (ENU). The resulting primary tumors as well as isogenic transplantation tumor lines and clonal cell lines derived therefrom were examined for their content of the brain specific protein 14-3-2 by a quantitative microcomplement fixation assay. The content of S-100 protein in the samples studied is given as well. Some of the tumors of glial or Schwann cell origin did contain 14-3-2 protein ranging from 0.6 to 1.5 mug 14-3-2 per mg total soluble protein. Our experiments also showed that the ability of a tumor to produce this specific protein is transplantable over a series of subcutaneous isogenic transplantations while in the transplantation tumors the content of this protein seemed to be reduced. We were not able so far to find a correlation between the morphology of a tumor and its capability to produce a specific protein. The clonal cell line RN2 of Schwann cell origin which has been previously described in detail contained both the brain specific proteins 14-3-2 and S-100 in comparable amounts ranging from 0.3 to 0.6 and from 0.4 to 1.0 mug specific protein per total soluble protein respectively.


Stability of distance between structured groups in a social organism: empirical research. The working hypothesis at the basis of the research is that in the development process of a social body the distance between structural groups of persons remain constant. The structural groups considered are men, women and a selected group of women (Soroptimists). The inquiry was carried out in 15 European countries in 1972. The total number of interviews was 4200. The six variables considered in the inquiry are the attitudes in respect of work, family, education, free time, sex and politics. The discriminatory analysis techniques are: entropy and factor analysis. Results seem to confirm the hypothesis of stability between groups and of countries between one another.


Retinol and retinyl esters in pigment epithelium of rats with inherited retinal degeneration. A comparative study of the retinol and retinyl ester concentrations was performed in the retinal pigment epithelium of the normal and affected rats. Our findings indicate that in dystrophic rat retinol content increases, whereas the amount of retinyl esters is always lower than normal. An hypothesis can be made on the deficiency of enzymic activities which regulate retinol retinol and retinyl esters levels in the pigment epithelium.


Dense particles in subcutaneous collagen fibrils. Electron microscopy of unstained, fresh air-dried spreads of the subcutaneous connective tissue disclosed dense particles (6-20 nm in diameter) at the dark bands of collagen fibrils with 67 nm periodicity. The particles appear to consist of chlorides from the X-ray microanalysis of collagen fibres.


Effects of alanine, glycine and glutamic acid on nitrogenous excretion by Amphiuma means liver in organ culture. High concentrations (10 mM) of alanine, glycine, and glutamic acid in the culture medium had no effect on urea production in Amphiuma means liver in organ culture. Ammonia production was increased in media containing added alanine and glycine, but reduced in medium with added glutamic acid.


Field testing of cis-11-tetradecenal as attractant or synergist in Tortricinae. Field studies have shown that cis-11-tetradecenal is an effective attractant for male Choristoneura conflictana, a pest of aspen. These studies also indicate that cis-11-tetradecenal is probably a secondary component in the sex pheromone systems of Choristoneura rosaceana and Choristoneura fumiferana.


Long-chain (Z)-9-alkenes are "psychedelics" to houseflies with regard to visually stimulated sex attraction and aggregation. Three different tests on houseflies (Musca domestica L.) revealed that both pheromone-free pseudoflies and male partner flies exhibit in the presence of mixtures of long-chain (Z)-9-alkenes or pure (Z)-9-tricosene enhanced releasing effects for two optical cues, which stimulate male houseflies to mating strikes and houseflies of both sexes to aggregation.


Sodium pumps and galactose transfer in the short-circuited small intestine. In a short-circuited preparation of rat jejunum, there are two sodium pumps, one electrogenic and the other neutral. When energy sources are limited, the total sodium transfer is limited. In the presence of a non-metabolized actively transferred hexose, the electrogenic pump is preferentially used. The neutral sodium pump is only able to function when additional energy is available.


Contraction of myoepithelial cells in secreting submandibular glands of dogs. In slowly secreting submandibular glands of dogs, a sympathetic effect on myoepithelial cells was demonstrated as an acceleration of the flow, followed by retardation, on short-lasting sympathetic stimulation, particularly after beta-adrenoceptor-blocking drugs.


Physiological studies on the effects of nutritional imbalance on the central nervous system. II. Effects of thiamine deficiency on oxidative enzymes in the brain of chicken, Gallus domesticus. The activitiy levels of succinate dehydrogenase, glutamate dehydrogenase and pyruvate dehydrogenase in the fore, mid and hind brain regions of the thiamine deficient chicken, Gallus domesticus were determined. The activity levels of succinate dehydrogenase and glutamate dehydrogenase in all the 3 regions of brain showed augmentation on inducing thiamine deficiency. In contrast the activity levels of pyruvate dehydrogenase decreased in the brain of thiamine deficient animals. It is suggested that these changes in the oxidative enzymes indicate disturbance caused in the operation of the tricarboxylic acid cycle in thiamine deficiency.


Rhythmic cerebellar and cortical electric activity in tetanus intoxicated rabbits. Intravenously injected tetanus toxin induced general tetanus within 12 to 37 h. The EEG of precentral, parietal, and occipital areas of the cerebellum revealed a highly rhythmic activity. In local tetanus of the limbs or in brainstem tetanus this rhythm could not be registered.


Potentiation of ethanol narcosis by dopamine- and l-DOPA-based isoquinolines. The isoquinolines, salsolinol and 3-carboxysalsolinol, prolong ethanol-induced narcosis in mice. Pretreatment with carbidopa increases the effect of 3-carboxysalsolinol but not of salsolinol. These results suggest that ethanol sleeping-time potentiation by l-LOPA may involve a partial conversion to the isoquinoline in vivo. A central depressant action of salsolinol or the 3-carboxy analogue is suggested.


Antitumor activity of the Isodon diterpenoids: structural requirements for the activity. A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.


Lithium effects upon components of activity in rats. When lithium chloride was administered to rats several changes occurred in a number of components of activity, some of which were sex-related. There was a reduction in both ambulatory and rearing activity and in behaviour associated particularly with the mouth and nose. The findings are related to a suggestion that lithium effects on behaviour may be more subtle than hitherto thought.


The action of substance P on mesencephalic reticular and substantia nigral neurones of the rat. Extracellular recordings were made from neurones in the mesencephalic reticular formation and substantianigra of the rat which was anaesthetized with urethane 1.5-2 g/kg i.p. Out of 44 cells tested 42 were excited by Substance P applied iontophoretically and in some cases this excitation was rapid. Evidence is presented for Substance P as a putative excitatory transmitter onto reticular and nigral neurones possibly released from primary sensory afferents.


Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4'-fluorobiphenyl)acetamide. Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4'-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy.


Uptake of L-glutamate and L-aspartate in neurones and glial cells of cultured human and rat spinal cord. Autoradiographic investigations on the uptake of L-glutamate and L-aspartate have shown that the amino acids were taken up by neurones as well as by glial cells of cultured human and rat spinal cord. The activity of glutamate and aspartate varied considerably between individual neurones, whereas glial cells showed a more even distribution of the labelled amino acids. Our results suggest that both neurones and glial cells are involved in the uptake of amino acid transmitters.


Deciduoma formation in rats with cornified vagina. In female rats given a single injection of 1.25 mg 5 alpha-dihydrotestosterone during neonatal life, reactivity of the vaginal mucosa to hormones was permanently altered, so that the rats, when adult, could show vaginal cornification under the hormonic conditions supportive of development of deciduomata in the uterus.


Intrauterine device increases the fibrinolytic activity of the rat endometrium at deciduation, a new aspect of its contraceptive effect. The fibrinolytic activity of the endometrium of the two uterine horns in the rat was histochemically determined. One of the horns contained a plastic-IUD, the other served as control. The endometrium of the control horn was almost inactive in contrast with that of the IUD-horn in which fibrinolytic activity was apparent. The fibrinolytic activity induced by the IUD might be involved in the prevention of ova implantation.


[Neurosecretion and hydroelectrolytic regulation in Artemia salina (author's transl)]. The activity of Artemia protocerebral median neurosecretory cells is stimulated when animals are grown in media whose tonicity is lower than that of sea weater. The substance liberated by these cells could regulate the tonicity of the internal medium.


Host immune rejection of TA3 ascites carcinoma cells following administration of a water soluble carbodiimide. Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide-HC1. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of 60Co radiation.


Concentration of "available" unesterified cholesterol in human plasma as evaluated from inhibition of hemolysis by lucensomycin. The unesterified cholesterol content of plasma samples can be evaluated from the extent of inhibition of lucensomycin-induced hemolysis. The test measures, however, only the fraction of cholesterol which is available for interaction with lucensomycin, this availability being adversely  affected by high phospholipid-cholesterol ratios.


[Structure-activity relationship of human calcitonin. III. Biological activity of synthetic analogues with shortened or terminally modified peptide chains (author's transl)]. Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group.


Epilepsy in women. Oestrogen and progesterone plasma levels. Comparison is made between numbers of fits and estrogen, progesterone plasma values during the menstrual cycle of women with epilepsy. All six cycles in women with ovulation had a significant positive correlation between estrogen/progesterone ratio and scores of fits. Three periods without ovulation all showed a significant correlation to estrogen variations.


A method for automatic recording of serum lysozyme activity with the fragiligraph. A quick and simple method for the estimation of lysozyme activity using the Fragiligraph, was described. Diminution of turbidity in a suspension of Micrococcus lysodeikticus produced by the addition of standard lysozyme (hen egg white) or serum sample, was continuously recorded for 5 min by the Fragiligraph. The normal mean serum lysozyme activity value obtained by this method is 6,80 mug/ml +/- 1.85.


Triterpenes of toxic and non-toxic taxa of Lantana camara. The taxa of Lantana camara toxic to animals contain lantadene A lantadene B, whereas in two non-toxic taxa other triterpenes predominate. Several new triterpenes have been characterized. Contrary to earlier claims, lantadene A and to a lesser extent lantadene B are toxic when administered intraruminally to sheep.


Synthesis of ovulation-inhibiting compounds; structure-activity relationship. We describe the synthesis of some new derivatives of benzo(4, 5)cyclohepta(1, 2-b)thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds.


Direct fluorination of carcinogenic polycylic aromatic hydrocarbons. 6-Fluorobenzo(a)pyrene. Xenon difluoride reacts with benzo[a]pyrene(BaP) in dichloromethane solution in an open system to give 6-fluorobenzo[a]pyrene. This method constitutes a direct route to fluorine substituted carcinogenic polycyclic aromatic hydrocarbons.


NMR-studies of triiodothyropropionic acid in ethanol-HCl. The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.


Identification of uncommon amino acids in the lentil seed (Lens culinaris Med.). The fraction of the free basic amino acids in the lentil seed was shown to contain gamma-hydroxyarginine, gamma-hydroxyornithine and homoarginine besides the common amino acids. Similar distribution was found in 5 varieties of lentil, with hydroxyarginine and arginine dominating. The significance of these findings with regard to chemotaxonomy and lentil consumption is discussed.


Food-induced changes in UV-absorption spectra of isolated chromatin from liver of rats under controlled feeding schedules. We have measured the UV-spectra of liver chromatin extracted at 2 different times of day, corresponding to low or high rate of RNA synthesis from rats maintained under controlled feeding schedules. Results show that food intake does modify the UV-spectra of liver chromatin.


Sterility and lethality in crosses involving two translocation heterozygotes of the Germay cockroach, Blatella germanica (L.). Productivity in crosses involving two independent reciprocal translocations in Blattella germanica are reported. Lethal effects alone could not account for the reductions in hatch since completely unproductive crosses occurred frequently. The latter are attributed to the inability of reduced numbers of viable embryos to force open the egg case. The implications for genetic control of the joint dominant effects from embryonic trapping and translocation semisterility are discussed.


Differential effects of lipids on the osmotic fragility of lysosomes. The effect of a wide range of concentrations of oleic acid, oleyl alcohol and oleic acid methyl ester on lysosomal stability has been studied under both hypotonic and isoosmotic medium conditions. Both oleic acid and oleyl alcohol exhibited a biphasic interaction pattern with lysosomes; stabilizing at low concentrations and labilizing at high concentrations. Lysosome labilization by the ester required an initial lag period.


Isolation of a Soldado-like virus (Hughes group) from Ornithodorus maritimus ticks in Ireland. Three isolations of a virus of the Hughes group were obtained from seabird ectoparasites, Ornithodoros (Alectorobius) maritimus, on Great Saltee Island, Ireland. The agent is closely related to Soldado virsu, originally obtained from related ticks near Trinidad, West Indies, and represents the second recorded tickborne arbovirus in Ireland.


Adsorption of hepatitis B surface antigen to matrix-boudn long chain hydrocarbon structures. The binding of hepatitis B surface antigen (HBSAg) to various matrix bound long-chain hydrocarbon structures has been studied. It was found that HBSAg was strongly bound to straight hydrocarbon chains with more than seven carbon atoms. The adsorbents can probably be used for removal and/or detection of hepatitis B infectious material.


In vitro attachment of trypanosomes to plastic. Description of an in vitro system for the study of the attachment of trypanosomes to polystyrene flasks by means of hemidesmosomes. This type of attachment, whose significance is so far unknown, reproduces a natural stage in the life cycle of medically important trypanosomatid flagellates in their vector.


Nematidical activity of secondary and tertiary alkyl amides and amines. Several C11 to C15 amides and amines that disrupt growth in certain insects showed high nematicidal activity in direct contact tests. Two amides and 9 amines killed Panagrellus at 5-10 ppm. Of these, 1 amide and 3 amines killed Meloidogyne larvae at 20 ppm.


Trinucleate pollen in the genus Populus. It is shown by light microscopy and microspectrophotometry that several Populus species produce trinucleate pollen. Such pollen seems more widespread than previously acknowledged.


The suppression of mouse spontaneous locomotor activity by the ingestion of deuterium oxide. The spontaneous locomotor activity of the laboratory mouse is significantly depressed by the ingestion of deuterium oxide. The response, which is reversible, is a retilinear one with up to 70% reduction in activity with the administration of 25% heavy water.


Is glucagon involved in  cold acclimatization? Cold acclimatization in rats at 5 degrees C for 2 weeks caused a significant elevation of plasma glucagon concentration, accompanied by increased plasma FFA and glucose levels. Acute cold exposure at 5 degrees C for 5 or 60 min did not affect these parameters in plasma.


Increased erythrocyte permeability to Li and Na in the spontaneously hypertensive rat. Red blood cells incubated in a physiological medium in which Li replaces Na (LiPSS) gain Li in exchange for Na and K. The rate of Li uptake is modestly but significantly increased in the spontaneously hypertensive rat (SHR) at 37 degrees C and at 22 degrees C. The slow rate of Na gain and K loss during cooling at 2 degrees C was about doubled in unmodified whole blood samples from the SHR.


Carotid chemoreceptor influence on the cardiac sympathetic nerve discharge. Pure stimulation of carotid chemoreceptors induces, as a primary effect, the general spontaneous activation of both the cardioexcitatory and the cardioinhibitory medullary centres. These effects have been shown by keeping constant those parameters which, when modified, produced secondary effects hiding the investigated primary ones.


Hypoxia increases potassium efflux from mammalian myocardium. Hypoxia with or without simultaneous depletion of extracellular glucose increases 42K-efflux in cat and guinea-pig papillary muscles and bovine Purkinje fibres. The change observed in K efflux may be the result of an increase in K conductance at rest.


Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound. The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26-921, which inhibits LH-secretion and consequently ovulation, is described.


Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase. The LD50 of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in the acute toxicity of DMN.


DDT: the degradation of ring-labeled 14C-DDT to 14CO2 in the rat. Ring fission of p, p'-DDT was studied in the rat following a single oral dose of 0.74 mg/kg (1.04 muCi) of uniformly ring-labeled 14C-DDT. Expired air was passed through a solution of ethanolamine-ethylene glycol monomethyl ether (1:2) to trap 14CO2. A total of 1.6% of the radioactivity administered was recovered in the expired air collected continually for 10 days, indicating that while degradation of the phenyl moiety is not a major route of p,p'-DDT metabolism in the rat, it is equal to the urinary excretion. Nevertheless, these results represent the most radical change accomplished in vivo of a residual insecticide yet reported in mammals.


Ultrastructural autoradiographic study of the intracellular fixation of 3H-acrolein. The fixation of 3H acrolein in Dunaliella bioculata was followed by means of quantitative autoradiography electron microscopy. A fixation was observed mostly in the nucleus where aldehyde linkage remained stable at least for 48 hours.


Frequency of the various stages of the seminiferous epithelium in different strains of male mice. The duration of the various development stages of the seminiferous epithelium in different strains of male mice was determined by scoring the frequency distribution in randomly selected tubule cross-sections. The results obtained show a difference in the duration of the various stages between the different strains.


Further studies on the effect of 6-hydroxydopamine in retinal development. Neonatal albino rats treated with 6-hydroxydopamine revealed depletion of rhodopsin and monoamine oxidase in their retinas.


Intercellular bridges of chick blastoderm studied by scanning and transmission electron microscopy. Chick blastoderms were studied by scanning and transmission electron microscopy to identify by both methods a type of thread-like structure lying on the epiblast. The structure was identified by transmission microscopy as a long telophase bridge containing mid-body and spindle remnant. It appears to provide cytoplasmic continuity between only 2 cells.


On the formation of corpus Balbiani in the ovogonia of man and guinea-pig. Studies were conducted on the ovogonia of human embryos at the age of 33, 35 and 40 days. Myelin-like bodies in the nuclei and in the cytoplasm were observed. In other cases, the ovogonium contained 4-5 myelin-like bodies oriented round the centrioles. This is supposed to represent an early phase of corpus balbiani formation.


Melanogenic melanocytes in human sebaceous glands. Electron microscopic observations revealed for the first time a small number of active melanocytes synthesizing distinctive melanin-containing organelles (melanin granules)in the ducts and acini of human sebaceous glands.


Utilization of ascorbic acid during post-embryonic development of chick skeletal muscle. Ascorbic acid is utilized during the post-embryonic differentiation of skeletal muscle fibres in chick. While the fibres lose their heterogeneity with regard to ascorbic acid, they continue to exhibit differences in their metabolic rates in terms of the succinate dehydrogenase activity throughout life.


Familial association in serum IgE levels. The serum IgE levels measured by RIST correlated closely with those obtained by the single radioimmunodiffusion method. Values for husband and wife were closely related as were those between father and daughter but in contrast to previous observations no significant relationship existed between IgE levels for mother and son.


Production of heteroagglutinins in haemocytes of Leucophaea maderae L. It was our purpose to study the immunological activity of circulating fluid cells in the blattoid insect Leucophaea maderae L. These cells are generically called haemocytes; after a preliminary morphological study under optical microscope, they were treated with anti-heteroagglutinins serum marked with fluorescein isothiocyanate. Thus, it was possible to show the presence of heteroagglutinins into the cytoplasm, as regards one group of haemocytes, and on the cell membrane for the second group.


Alpha adrenergic control of growth hormone in adult male rats. Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 mug/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central alpha-adrenergic stimulation resulting in an increased GH secretion is one important mechanism in the regulation of this hormone in the rat.


A preparation for the study of muscle metabolism during rest and activity. A method for the investigation of metabolism in the isolated rat extensor digitorum longus muscle has been described. This muscle was shown to be suitable for investigations of skeletal muscle metabolism during rest and activity.


Abortion need and services in the United States, 1974-1975. More than one million legal abortions were performed in the United States last year--but one-half to three-quarters of a million women in need of abortion services were still unable to obtain them. Ninety percent of all abortions are now performed in the woman's home state, but services are still highly concentrated within states--typically in one or two metropolitan centers where most services are provided by nonhospital clinics. Only one-fourth of hospitals-and fewer than one-fifth of public hospitals-provide any abortion services. Many poor, rural and teenage women who can least afford to travel to obtain legal abortions will continue to be denied access to the services they want and need.


Successful use of the diaphragm and jelly by a young population: report of a clinical study. In the largest contemporary study of diaphragm use in the United States, the authors examine the experience of 2,168 women who selected this method of contraception at the Margaret Sanger Research Bureau over a recent two-year period. Eight in 10 of the study group were younger than 30 years and three in 10 were aged 21-24. Seven in 10 had never been married and the same proportion had never been pregnant. Accidental pregnancies in the first 12 months of use ranged from a low of 1.9 per 100 users younger than 18 years old to a high of 3.0 among 30-34-year-olds; and more than eight in 10 were still using the diaphragm at the year's end. These rates compare favorably with those reported for the pill and IUD in other clinical studies.


[Pharmacological study of a series of indandione derivatives proposed as anti-inflammatory agents]. A variety of aryl-indandiones were tested in rats and mice with the aim of separating the antiinflammatory activity from anticoagulant and ulcerogenic activity. Previously reported antiinflammatory activity was confirmed. All compounds also inhibit blood coagulation. However, compounds (II) and (IV) did not show ulcerogenic activity.


[Preparation of some pyrido (2,3-e)-1,4-diazepines]. By treating pyrido (2,3-e)-1,4-diazepinones with alkyl halides, N4-alkylpyrido (2,3-e)-1,4-diazepines were obtained. In addition a number of N1-alkylpyrido (2,3-e)-1,4-diazepines were prepared from alkyltetrahydronaphthyridinones by the Schmidt reaction. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.


[Phytotoxicity of hydrazones of aromatic aldehydes]. A series of hydrazones of aromatic aldehydes (B) was prepared and tested for phytotoxicity. These compounds are bioisosters of 1-aryltriazenes (A) which were found to possess interesting phytotoxic properties in a previous research. The substances studied (Tables I leads to III: compounds(I leads to CLXXX)) some of which were previously unrecorded, were prepared by the usual procedures from the required aldehyde and hydrazine derivative. The phytotoxicity of all the compounds was studied using seven representative species in both pre- and post-emergence tests at a dose of 6 kg/ha. It was found that this class of compounds shows phytotoxicity by absorption through the foliage with specificity for Amaranthus retroflexus L. The only exceptions are compounds where the aryl residue is 2,6-dichlorophenyl; these compounds show wide spectrum of phytotoxicity by absorption through the leaves.


[Phytotoxic activity of triazene derivatives. VI. 1-aryl-3-arylalkyl-3-alkyltriazene derivatives]. A series of of 1-aryl-3-arylalkyl-3-alkyltriazenes (B) was prepared and studied for phytotoxic activity. The previously unknown substances [Table I: substances (I leads to XVI)] were prepared by condensation of the appropriate diazonium salt with the required secondary amine in an alkaline medium and were tested against five representative plant species in both pre- and post-emergence tests at a dose of 6 kg/ha. All the substances studied were inactive in pre-emergence tests. However most of the compounds showed phytotoxic activity by absorption through the foliage. This activity was not very pronounced and always lower than triazene analogs previously studied (type A compounds) which have no aralkyl residue on nitrogen 3.


Radiopaque contrast media. XXXIV - Derivatives of omega-(3-amino-2,4,6-triiodophenoxy)alkoxyalkanoic acids. A series of new oral cholecystographic contrast media with promising characteristics is obtained after the study of the relationships among molecular structure, tolerability, biliary and urinary excretion, as well as gallbladder opacification. The synthesis of this series is described. Particularly good tolerability, high biliary excretion and excellent roentgenographic findings were achieved with compound (IX) (iopronic acid). This contrast agent was selected for a more detailed study of toxicology, pharmaco-kinetics, metabolism and experimental radiology.


[Negative geotropic effect and phytotoxicity of N-quinolinphthalamic acids and allied substances]. N-Quinolinphthalamic acids and allied substances have been prepared and studied for negative geotropic effect and phytotoxic activity. The substances (Tables I leads to III) prepared by fusion of the required anhydride and amine were tested to evaluate the negative  geotropic effect on germinating roots of Lens esculenta Moench s.1. and phytotoxicity in both pre- and post-emergence tests against five representative weed species at a dose of 6 kg/ha. It was found that substances (I), (VII), (VIII) and (IX) showed negative geotropic effect of the same order of magnitude as that of the reference substance (alpha-naphthylphthalamic acid). Substances (VII), (VIII) and (IX) proved highly active in the phytotoxicity tests. The simultaneous appearance of geotropic and pre-emergence phytotoxic activity seems to be connected with the presence of an 8-quinoline residue on the amide nitrogen.


[Adrenergic reactivity of the gastro-intestinal tract. II. Colon of the guinea pig and cecum of the mice]. A study has been made of the alpha- and beta-adrenoreceptors in the guinea pig colon and the mouse caecum using noradrenalina as agonist and alpha- and beta-adrenolytics separately or together. In the guinea pig colon alpha-adrenolytics used alone did not alter the action of noradrenalin: one beta-lytic (propranolol) used alone has slight non dose-dependent action. The alpha-lytics used together with beta-lytic strongly potential their effect. These results are interpreted as indicating that the preparation contains alpha-receptors as well as beta-receptors; activation of the alpha-receptors is observed only when the beta-mimetic effect of noradrenalin is inhibited. In the mouse caecum alpha-lytics prove devoid of effect either alone or when associated with beta-lytics; it is deduced therefore that this preparation contains only beta-receptors.


Physiological disposition of a new diuretic compound, 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (M.G. 13054 - fenquizone), in the dog. The absorption, excretion and metabolism of a new diuretic compound, 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (M.G. 13054), after oral administration to the dog have been studied. The results can be summarized as follows: 1) M.G. 13054 given orally to dogs is quickly absorbed. 2) The maximal blood levels are reached within the 3rd hour after the administration and remain appreciable (10% of the maximal values) till the 12th hour. 3) Fecal and urinary excretion is rapid and 94% of the product administered is excreted in the first 48 hours following treatment. 4) The product does not seem to be tightly bound to plasma proteins. 5) M. G. 13054 does not seem to be metabolized to any appreciable extent.


[Synthesis of long chain alkyne and alkene ketoalcohols and their derivatives]. A description is given of the synthesis of the acetylenic alcohol with 16 carbon atoms (V) starting from 6-ethylendioxy-4,4-dimethyl-2-heptyne (III) and valeraldehyde followed by reduction with Raney-nickel and lithium in liquid ammonia.


The structure of lymphatic capillaries in lymph formation. The lymphatic vascular system consists of endothelial lined vessels which begin as blind-end tubes or saccules that are located within the connective tissue areas. This system serves as a one-way drainage apparatus for the removal of diffusible substances as well as plasma proteins that escape the blood capillaries. If permitted to accumulate, these escaped components would deplete the circulatory system of its plasma colloids and disrupt the balance of forces responsible for the control of fluid movement and the exchange of gases and fluids across the blood vascular wall. The lymphatic capillaries are strategically placed and anatomically constructed to permit a continuous and rapid removal of the transient interstitial fluids, plasma proteins, and cells from the interstitium. Structurally the lymphatic capillaries consist of a continuous endothelium that is extremely attenuated over major aspects of its diameter, except in the perinuclear region which bulges into the lumen. These vessels lack a continuous basal lamina and maintain a close relationship with the adjoining interstitium by way of anchoring filaments. The adjacent cells are extensively overlapped and lack adhesion devices in many areas. When electron-opaque tracers are injected intravenously (i.e., horseradish peroxidase and ferritin), subsequent electron microscopic examination of tissues reveals the presence of tracer particles within the interstitium and the lymphatic capillary lumen. These particles gain access into the lymphatic capillaries via two major pathways: 1) the intercellular clefts of patent junctions and 2) plasmalemmal vesicles (pinocytotic vesicles). Another salient feature of the lymphatic endothelial cell includes the presence of numerous cytoplasmic filaments, which are similar in morphology to the actin filaments observed in a variety of cell types. The ultrastructural features of the lymphatic capillaries are discussed in relation to their role in the removal of interstitial fluids and particulate matter, and in the formation of lymph.


Tissue pressures and fluid dynamics in the kidney. The kidney has several characteristics which make renal pressures and fluid dynamics unique when compared to other organs. Renal blood flow is roughly 100 times that of skeletal muscle. The renal circulation consists of two distinct capillary beds in series: a high pressure system in the glomerulus that favors filtration and a low pressure system in the peritubule network that favors reabsorption. The hydrostatic pressure in the glomerular capillary is 4-6 times higher than the hydrostatic pressure in the peritubule capillary so that approximately 25% of the plasma is filtered. The bulk of the filtrate is subsequently reabsorbed by the peritubule capillary network. Micropuncture techniques have been used to obtain quantitative measurements of the pressures and fluid dynamics of the peritubule microcirculation. The net force for uptake of all the fluid reabsorbed by a single proximal tubule up to the point of micropuncture is 21 mm Hg acting over a capillary bed with a permeability surface area product of 2 nl/min per mm Hg. In contrast to subcutaneous tissue and muscle, the renal interstitial fluid pressure is positive. The consequence of a positive interstitial fluid pressure is that normal lymph flow is relatively high and changes in interstitial fluid pressure have relatively little effects on lymph flow.


Glycine-serine interrelations in the chick. Glycine and serine are involved in numerous important functions in the body in addition to protein synthesis. Glycine is synthesized by higher animals; however, the rate is not adequate to support maximal growth of the chick. Studies indicate that chicks fed a glycine-serine free crystalline amino acid diet grow at approximately 80% the rate of chicks fed the same diet supplemented with glycine. An equimolar quantity of L-serine has been shown to support equal chick performance as glycine, thus indicating that serine conversion is adequate to meet the dietary need for glycine. The serine-glycine interconversion is catalyzed by the folic acid containing enzyme sering hydroxymethyltransferase, and a deficiency of this vitamin decreases the effectiveness of serine in meeting the chick's dietary need for glycine. Studies with chicks fed normal and high levels of a crystalline amino acid mixture devoid of glycine and serine indicate that the chick has the metabolic potential to synthesize more of these two amino acids than should be required for normal growth. The observed dietary response to glycine or serine or both indicates, however, that this synthetic potential is not being utilized.


Nutritional and metabolic interrelationships of arginine, glutamic acid and proline in the chicken. Proline satisfies by a narrow margin the criterion for dietary essentially for the chick. It is estimated that the chick may synthesize 80-90% of the total proline needed for growth. Although the metabolism of arginine, ornithine and glutamic acid is expected to give rise to proline, dietary supplements to these amino acids are relatively ineffective in reducing the proline requirement of chicks. Studies of the efficacy of dietary ornithine for growth, and tracer studies using L-(5-3H)arginine indicate that the conversion of ornithine to proline in vivo is limited, and the amount of proline synthesized from arginine is but a small fraction of that needed for growth. The limiting processes in proline synthesis from glutamic acid and ornithine are not known. In Escherichia coli, where the biosynthetic pathway from glutamate to proline has been elucidated, a glutamate kinase, NADP-dependent delta1-pyrroline-5-carboxylic acid (P5C) dehydrogenase and P5C reductase catalyze proline synthesis. P5C reductase is present in the soluble fraction of chicken liver and kidney. An NADP-dependent P5C dehydrogenase activity has also been observed in this fraction of liver. Further studies are required to assess the importance of these enzymes in proline biosynthesis and to determine the limiting process in proline formation in the chicken.


Clinical experience with metiamide.

Clinical experience with metiamide. The new histamine H2-receptor antagonist, metiamide, was shown to inhibit acid and pepsin secretion in gastric secretion studies performed on patients suffering from peptic ulceration. The new drug was administered intravenously in these experiments, but effective plasma levels could also be produced by oral administration. When symptomatic patients were treated with the drug nearly all experienced marked symptomatic relief, and there was some evidence that ulcer healing occurred during treatment. When the drug was withdrawn symptoms tended to return. No toxic reactions were encountered in this trial. Double-blind studies are now being made in Britain to establish the place metiamide may have in the treatment of duodenal ulceration.


The luteal phase defect.

The luteal phase defect. In summary, the luteal phase defect is a deficiency of corpus luteum progesterone steroidogenesis, either in amount or duration, or both. The clinical manifestations include either primary infertility or repeated first trimester abortions. The diagnosis can only be made clinically on the basis of a well-timed endometrial biopsy that is read histologically as 2 or more days out of phase with the next period in at least two cycles.


Predetermination of ovulation timing by luteinizing hormone assay. A modified rapid,solid-phase radioimmunoassay for serum luteinizing hormone requiring only 1 1/2 hours of incubation is presented. The method has been used to predetermine the time of ovulation in six infertile patients. Its advantages are presented in these cases. The simplicity and accuracy of the method make it practical, and it can serve well in the management of infertility.


High doses of estrogens do not interfere with the ovulation-inducing effect of clomiphene citrate. A sequential regimen of 100mg of clomiphene citrate (days 5 to 9) and 180 mug of ethynyl estradiol or 7.5 mg of conjugated estrogens (days 10 to 16 or 17) was given to 29 infertile patients. Eleven patients conceived. Four pregnancies terminated as early abortions; the remaining seven went to term. In four cases an ovarian hyperstimulation syndrome developed.


Clomiphene-regulated ovulation for donor artificial insemination. Seventeen couples with male-caused infertility requested donor artificial insemination between January 1, 1973, and December 31, 1974. All of the women were evaluated prior to the inseminations and were found to be ovulatory. They were treated with clomiphene, citrate 50 mg/day for 5 days beginning on day 4,5, or 6 of a menstrual cycle, and scheduled for two inseminations on the 5th and 7th days after completion of the clomiphene regimen. Fresh semen placed in cervical cups was used for the inseminations. The procedure was repeated in the following months until conception occurred.


Presence of prolactin in human cervical mucus. The presence of prolactin in human cervical mucus was demonstrated by radioimmunoassay. The levels of prolactin in cervical mucus were significantly higher (260 ng/ml +/- 47.5 SE) than those in sera of normally menstruating women (30.28 ng/ml +/- 2.0 SE).


Antispermatozoal immunoglobulin G in the sera of subfertile men. Sera were obtained from seven men who had not fathered a child and whose semen showed self-agglutination of spermatozoa. These samples of sera produced considerably more immobilization and agglutination of spermatozoa and positive passive hemagglutination tests than did sera from men whose semen showed less than 10% self-agglutination of spermatozoa.


The effect of steroid hormones on motility and selective migration of X- and Y-bearing human spermatozoa. Motility and selective migration of X- and Y-bearing human spermatozoa were studied in the presence of physiologic levels of sex steroid hormones (17beta-estradiol; estriol, 0.5 ng/ml; testosterone; progesterone; lynestrenol; and norgestrel, 5 ng/ml) and 200-fold higher concentrations. Estrogens and, to a smaller extent, testosterone accelerated spermatozoal migration, while gestagens had an inhibitory effect. 17beta-Estradiol was most effective in stimulating the motility of human spermatozoa, while norgestrel caused the strongest inhibition of forward movement. Migration of X- and Y-bearing spermatozoa was most significantly altered after longer distances of migration, shown by an increase in the percentage of Y-bearing spermatozoa from 43.7% to 63.3% at a distance of 90 mm. However, prolongation of migration time to 36 hours caused a reduction in the percentage of Y-bearing spermatozoa at the 90-mm distance, from 63.3% to 46%. Specific differential effects of sex steroid hormones on the pattern of selective migration and the distribution of X- and Y-bearing spermatozoa were not observed.


Changes in the sensitivity of adrenergic receptors in the oviduct during early gestation in the rabbit. There is evidence to indicate that the transport of an egg through the rabbit oviduct is controlled through an interaction of the sympathetic nervous system and ovarian hormones. The effect of norepinephrine (NE) on the contractility of the oviduct during the first 8 days of gestation was studied using the rabbit perfused oviduct. The sensitivity of the alpha-adrenergic receptors of the oviduct to NE decreased progressively during early gestation. This was reflected in a potency change and a decrease in the maximal response obtained. These data support the concept that an isthmic sphinctering effect mediated by the autonomic nervous system may play a role in the regulation of egg transport through the oviduct. Blood pressure responses to NE did not change during early pregnancy except that the responses to NE were significantly enhanced immediately after mating. This suggests that the sensitivity changes to autonomic agents during early gestation may be selective for reproductive tissues.


Demonstration of postovulatory sphincter action by the isthmus of the rabbit oviduct. Doughnut-shaped, carbon-impregnated rubber microtransducers calibrated to measure changes in diameter are used to demonstrate the occurrence of a sphincter action in the isthmus of the rabbit oviduct following human chorionic gonadotropin (HCG)-induced ovulation. The postovulatory constricture of the isthmus is temporal and coincides with the period when ova are retained in the oviduct. The mean change in diameter of transducers positioned within the lumen of the isthmus in rabbits treated with HCG are significantly different from mean changes observed in nontreated control rabbits when tested at 8-hour intervals over a 104-hour period. The difference is due to a statistically significant decrease in transducer diameter which occurs between 16 and 56 hours post-HCG injection. Treatment with exogenous estrogen in combination with HCG enhances both the magnitude and duration of this constricture. Significant differences occur between 8 and 104 hours. Pretreatment with progesterone prior to HCG-induced ovulation completely blocks the constricture of the isthmus. Both oviducts exhibit identical responses following HCG-induced ovulation. Sphincter action is not confirmed to a small localized segment of the isthmus but occurs over a wide area.


Effects of intrauterine devices on nuclear deoxyribonucleic acid metabolism in rabbit blastocysts: an autoradiographic study. A metabolic parameter, DNA synthesis, was measured in rabbit blastocysts exposed to Silastic intrauterine devices (IUDs) and compared with those without IUD exposure. Autoradiographic detection of 3H-thymidine uptake showed that the IUD-exposed blastocysts contained fewer labeled cells than their IUD-free equivalents. The depressed DNA synthesis may be caused by either a block in the cell cycle or a block in DNA synthesis itself. Either way, the result could be consistent with the observation that embryo deaths occur at all growth stages, preimplantation, during implantation, and postimplantation.


The effect of centchroman on serum luteinizing hormone in normal males. Elevation of serum luteinizing hormone levels was observed in five normal male volunteers while they were taking Centchroman. This effect resembles that of clomiphene and suggests a new biologic potential of Centchroman.


Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs. The suppressive effect of insulin on hepatic glucose production is generally recognized. Though it is well established that this effect is at least partially due to inhibition of glycogenolysis, controversy still exists about insulin's effect on gluconeogenesis. The present study was undertaken to determine whether insulin could affect gluconeogenesis from alanine in the intact dog and to compare the effect of insulin on glycogenolysis and gluconeogenesis. In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 mu Ci./kg., was infused over 110 minutes. A constant insulin infusion at either 1 or 5 mU./kg./min. was begun at 50 minutes, and blood glucose concentration was maintained by a variable glucose infusion. When insulin was infused at 1 mU./kg./min., resulting in plasma immunoreactive insulin (IRI) levels of 73 +/- 10 muU./ml., the net splanchnic glucose production (NSGP) was suppressed from 2.7 +/- 2 mg./kg./min. to virtually zero. In constrast, this small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 +/- 0.3 mu mol/min.). Insulin infused at 5 mU./kg./min. resulted in IRI levels of 240 +/- 25 muU./ml. This higher insulin concentration was associated with a marked suppression of both the NSGP (100 per cent) and the conversion of plasma alanine to glucose (90 per cent) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU./kg./min. were associated with a 35 per cent fall in immunoreactive glucagon levels. These data demonstrate that (1) glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations, (2) gluconeogenesis could be suppressed by insulin but only at higher insulin concentrations, (3) this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and finally, (4) that insulin can suppress glucagon in the absence of hyperglycemia.


Assessment of peripheral vascular disease in patients with diabetes. Two case studies. This report proposes that perfusion scanning in combination with arteriography be included in the diagnostic work-up of the diabetic patient who, because of peripheral vascular complications, is a candidate for surgery. Two cases are reported which illustrate the extremes of the findings: abnormal arteriogram-normal scan indicating large-vessel disease without significant small-vessel involvement. It is suggested that these patients are candidates for vascular reconstruction. The other extreme is the normal arteriogram-abnormal scan indicating small-vessels disease without significant large-vessel involvement. It is apparent that these patients are not candidates for vascular reconstruction.


Arginine-stimulated hyperglucagonemia in diabetic Pima Indians. Groups of 27 nondiabetic Pima Indians, 34 nondiabetic Caucasians, and 12 diabetic Pima Indians with recent onset of their disease received an arginine infusion to determine if (1) nondiabetic Pima Indians and Caucasians had a similar glucagon response to arginine and (2) diabetic Pimas had excessive glucagon response to arginine as reported in other racial groups. The fasting glucagon levels in the three groups were not significantly different. During arginine monochloride infusion (5 mg./kg./minute for 40 minutes) the diabetic Pimas had glucagon levels significantly higher at 10 minutes and at all sampling points thereafter than the normo-glycemic Pimas. Plasma insulin levels also increased during the infusion but, notably, never differed significantly between these two groups. There was no significant difference in the glucagon levels at any sampling point between the nondiabetic Pimas and Caucasians. The differences in glucagon levels between the nondiabetic and diabetic Indians are similar to those differences reported between diabetic and nondiabetic subjects of other racial origins.