Cerebellar stimulation: regional effects on a thalamocortical system.

Regional effects of electrical stimulation of the cerebellar surface were quantitatively analyzed. Computer controlled stimulus sequences were delivered to ventrolateral thalamus and evoked responses recorded from ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were produced with an on-line computer, and their modification by cerebellar stimulation was determined. The results of electrical stimulation of the cerebellar surface were: (1) depressed excitability from paramedian lobule and lobulus simplex; (2) uniquely elevated thresholds from paramedian lobule; and (3) a profound and long-lasting depression of excitability following termination of lobulus simplex stimulation. In comparison with our anticonvulsant drug studies, these data suggest that cerebellar surface stimulation has a far greater capacity to control excitability and threshold responsiveness of thalamocortical systems. Cerebellar electrode placement and temporal pattern of stimulation appear to be important factors in the production of antiepileptic effects.


Prevalence of epilepsy in children of Melipilla, Chile.

The prevalence of epilepsy among children born in 1966 and reaching the age of 9 years during 1975 was investigated in Melipilla, Chile, using questions similar to those used by Rose et al. (1973). Of 2,104 potential respondents, 2,085 were interviewed. A sample of 593 children received neurological examination and 455 received an electroencephalogram. The prevalence rates for epilepsy were higher than those reported in two American studies using the same methodology. The possibility of socioeconomic factors to account for these differences was considered. Prevalence rates for simple febrile convulsions and minimal brain dysfunction were similarly calculated.


Slow depolarizing potentials in "epileptic" neurons.

Slow depolarizing potentials following penicillin-induced epileptiform bursting were recorded intracellularly from cat cortical neurons in vivo and guinea pig hippocampal neurons in vitro. In in vitro experiments, it was shown that blocking potassium conductance with tetraethylammonium resulted in epileptiform bursting and after potentials similar to those seen with penicillin application. It is hypothesized that an abnormality in potassium conductance, and a resulting increase in calcium influx, could be responsible for the long depolarizations characteristic of some neurons in epileptic foci.


EEG operant conditioning for control of epilepsy.

We report the results of 23 severely epileptic patients who were given EEG feedback training. The paradigm reinforced the patients' 18 Hz activity over the scalp approximation of their focus while suppressing temporalis EMG and low frequency EEG activity. In contrast to other studies using EEG feedback, only 43% of patients showed significant changes in seizure occurrence and a lesser number were felt to have benefited clinically. None of our neuropsychological test parameters were helpful in identifying (prospectively or retrospectively) patients most likely to respond to this treatment. Although a few patients were significantly helped by this training, the mechanism for this effect is unclear.


Evidence for the epoxide-diol pathway in the biotransformation of mephenytoin.

A dihydrodiol metabolite of mephenytoin (5-dihydroxycyclohexadienyl)-5-ethyl-3-methylhydantoin and other mono- and dihydroxylated and N-demethylated metabolites were identified in urine from a male epileptic patient receiving therapy with mephenytoin (300 mg/day). Metabolites, extracted from urine before and after enzymatic hydrolysis, were derivatized with a trimethylsilyl reagent and analyzed by combined gas chromatography and mass spectrometry. Two previously unreported metabolites were characterized: 5-ethyl-5-(di-hydroxyphenyl)-3-methylhydantoin and 5-ethyl-5-(hydroxy-methoxy-phenyl)-3-methylhydantoin. The structures of several other metabolites were confirmed: N-demethylmephenytoin, 5-ethyl-5-hydroxyphenylhydantoin, 5-ethyl-5-hydroxyphenyl-3-methylhydantoin and mephenytoin dihyrodiol. The dihydrodiol metabolite was of special interest since it was probably produced via an epoxide intermediate, 5-(epoxy-cyclohexadienyl)-5-ethyl-3-methylhydantoin. Previous reports have demonstrated that epoxides of this structural class are extremely reactive compounds, capable of alkylating biologic macromolecules. Covalent binding of the mephenytoin epoxide to macromolecules may be an important factor in the production of adverse and sometimes fatal side effects observed in patients receiving long-term therapy with mephenytoin.


Predicting serum vitamin E concentrations from the age of normal and anticonvulsant drug-treated epileptic children using regression equations.

Serum vitamin E was assayed in 100 patients who were apparently normal, with no medical problems and on no medication, and whose ages ranged from 2 to 12 years. Serum vitamin E was also assayed in 100 patients with grand mal convulsive disorders, on anticonvulsants, but on no other drugs, with no gastrointestinal problems and in a similar age range. In the 100 control children, there was a tendency for serum vitamin E to increase with age. Serum vitamin E concentrations in 100 anticonvulsant drug-treated epileptic children were significantly lower than in the control group and did not increase with age. In the control group, a regression analysis was used to predict serum vitamin E concentrations in different age groups. This information would be useful for population and metabolic studies of serum vitamin E concentrations.


Dipterex teratogenicity in the rat,  hamster, and mouse when given by gavage.

Dipterex was teratogenic after administration by gavage (t.i.d.) at a dose level of 480 mg/kg-day to the CP rat on days 6 through 15 of gestation, but not when administered only on days 8 or 10 of gestation. A positive teratogenic response also occurred in the hamster after administration on days 7 through 11 of gestation at 400 mg/kg-day; the apparent no-effect level for the criteria studied was 200 mg/kg-day. Embryotoxicity, but not teratogenicity, occurred after administration of 400 mg/kg-day on day 8 of gestation. In both species, the teratogenicity seen was not merely due to reduced maternal food consumption during the period of exposure. The mouse was less susceptible to Dipterex than were the rat and hamster, but a significant increase in the incidence of cleft palates resulted from exposure on days 10 through 14, or on days 12 through 14 of gestation.


Study of nonionizing microwave radiation effects upon the central nervous system and behavior reactions.

The biologic effect of an electromagnetic field of a frequency of 2375 +/- 50 MHz was studied in rats and rabbits in specially constructed absorbant chambers. The results of the investigations have shown that microwave radiation of 10, 50, 500 mu W/cm2 for 30 days, 7 hr/day, causes a number of changes in bioelectric brain activity and also in behavioral immunological, and cytochemical reactions. It was found that levels of 10 and 50 mu W/cm2 stimulate the electric brain activity at the initial stage of irradiation, while a level of 500 mu W/cm2 causes its suppression, as seen from the increase of slow, high amplitude delta-waves. At 500 mu W/cm2 a decrease in capacity of work, in value of unconditioned feeding stimulus, in investigating activity, electronic irradiation threshold, and in inhibition of cellular and humoral immunity were also observed.


Effects of noinionizing radiation on the central nervous system, behavior, and blood: a progress report.

This paper presents a progress report on the U. S. research which has been designated as collaborative research with the Soviet Union to study the biological effects of nonionizing radiation on the central nervous system, behavior, and blood. Results of investigations to study the effects of microwaves on isolated nerves, synaptic function, transmission of neural impulses, electroencephalographic recordings, behavior, and on chemical, cytochemical and immunological properties of the blood are presented. Specifically, the effects of microwave exposure on chick brain and cat spinal cords, on EEG patterns of rats, on behavioral of neonatal rats exposed during development, on behavior of adult rats, on behavior of rhesus monkeys and on the pathology, hematology, and immunology of rabbits will be reported in a summary format. Much of the information is new and has not been published previously.


Study of the combined action of a group of chlorine derivatives of hydrocarbons entering the organism by inhalation.

The combined action of substances having a munidirectional toxic effect on the organism was studied for several typical chlorine derivatives of hydrocarbons (1,2-dichloropropane, 1,2,3,-trichloropropane, and perchloroethylene). Since a correct assessment of the combined action of substances is based on the comparison of the effect of mixed compounds and the effects observed for each component alone, research was conducted on each individual substances on the basis of the "concentration--time" relationship. The reaction of several mixtures of substances was also studied at various concentration levels, from high to low concentration levels of substances which are actually present in the atmosphere. Research result showed that the character of the mixture at both high and low levels of concentration was identical and approximate to the overall effects.


Scientific basis for the study of demineralization of highly mineralized water for use in public water supply systems.

New criteria (full physiological value and preservation of the properties of drinking water) are scientifically substantiated. Also discussed are indices (minimal admissible and optimal levels of basic water mineralization and calcium content, standards of microelements such as boron and bromine content, content of individual groups of microorganisms, water temperature) for evaluating the quality of demineralized water obtained from brackish and briny water (including water from the sea and ocean) by various methods which are designed for public water supply systems. Research results served as the scientific hygiene basis for the development of a new technology of obtaining drinking water. The necessity for developing a special quality standard for demineralized drinking water is shown.


Bioassay of complex mixtures derived from fossil fuels.

The conversion or processing of shale, coal, or petroleum involves elevated temperatures and altered pressures, and under these conditions polynuclear aromatic hydrocarbons are likely to form. Certain compounds of this type exhibit carcinogenic activity for a variety of organ sites in experimental animals and epidemiological evidence strongly implicates their role as carcinogens in man. It is then not unexpected that many liquid fractions derived from shale and coal are carcinogenic when subjected to bioassay. Benzo(a)pyrene, [B(a)P], is frequently considered to be an indicator substance. It is clear that when a small quantity of B(a)P is present in a fraction, the fraction will exhibit carcinogenic activity in a bioassay (mouse skin). However, it does not follow that the lack of detectable B(a)P insures that the fraction will be noncarcinogenic. Several fractions have been analyzed for their content of B(a)P and then subjected to bioassay. A method for testing complex mixtures for their carcinogenic potential is described. The carcinogenic potency of these fractions are compared to petroleum fractions.


Carcinogenicity of oil shale tars, some of their components, and commercial products.

Bioassays for carcinogenicity of various primary processing products (crude oils or tars) and commercial products obtained from Estorian oil shale have been carried out since 1951. The products (undiluted or diluted) were painted twice weekly 50 times on the interscapular area of the skin of random-bred or CC57Br mice. The products processed at high temperatures have a higher carcinogenic activity. Blends of products containing over 10% of high temperature crude oil (chamber furnace oil) have about the same carcinogenic activity as the latter. There is no strict correlation between the concentration of benzo(a)pyrene (BP) in oil shale products and their carcinogenic activity. Determination of BP in such products can serve as an approximate estimate of carcinogenic properties. The results of animal experiments with chromatographic fractions of the high temperature shale oil demonstrated the presence of compounds which lengthen the latency period of the carcinogenic effect of BP in the aromatic fraction of this oil as well as other carcinogens and compounds enhancing the activity of carcinogenic compounds. Under industrial conditions, contact of workers with carcinogenic shale oils can be reduced by means of coking the carcinogenic oils, which results in production of solid coke and of distillate which is recycled. Medical vaseline potentiates the carcinogenic action of BP and similar compounds. Dilution of shale oils with oils containing aliphatic hydrocarbons cannot be considered as diminution of the carcinogenic potency of these products.


Carcinogenicity studies of Estonian oil shale soots.

Several series of chronic experiments in white mice and white rats were carried out in order to determine the carcinogenicity of Estonian oil shale soot as well as the soot from oil shale fuel oil. All the investigated samples of soot showed a relatively low (from 14 to 1200 ppm) benzo(a)pyrene content. The benzene extract of oil shale soot, painted on the skin of white mice, proved to be strongly carcinogenic: in most of the animals skin tumors developed. The benzene extract of shale fuel oil exerted a considerably weaker carcinogenic action than the extract of soot of solid shale. The effect of oil shale soots as well as of tars extracted from oil shale soot on the bronchial mucosa and lung respiratory tissue was studied in white rats. Lung tumors were induced in a considerable number of cases in a series of experiments, where the tarry material from solid fuel soot, containing 1070 ppm benzo(a)pyrene, as a suspension in an aqueous solution of Tween 40, was administered by repeated intratracheal instillation. Lung tumor incidence among various control and experimental groups of rats is presented. The peculiarities of oil shale combustion are described.


Cocarcinogenicity of phenols from Estonian shale tars (oils).

Many phenols have carcinogenic activity. The Estonian shale oils contain up to 40 vol % phenols. The promoting activity after initiation of phenols of Estonian shale oils was tested in mice with a single subthreshold dose (0.36 mg) of benzo(a)pyrene. C57Bl and CC57Br mice were used in skin painting experiments. Weak carcinogenic activity was found in the total crude water-soluble phenols recovered from the wastewater of a shale processing plant. In two-stage experiments a clear promoting action of the total crude phenols was established, whereas the fractions A and B (training reagents), obtained by selective crystallization of the total phenols exerted a considerably weaker promoting action. Epo-glue, a commercial epoxy product produced from unfractionated crude phenols, had no promoting activity, which may be due to the processing of the phenols involving polymerization. The mechanism of action of phenols is not clear. According to some data from the literature, phenol and 5-methylresorcinol reduce the resorption speed of BP in mouse skin, causing prolongation of the action fo the carcinogen.


Mutagenic and carcinogenic properties of polycyclic aromatic hydrocarbons.

The rapid development of the chemical industry, combustion of fossil fuels, and smoking of tobacco have resulted in contact of the general population with benzo(a)pyrene and other carcinogenic aromatic hydrocarbons. Persons especially at risk occupationally are those engaged in thermal processing of oil shale, coal, and heavy residual petroleum. It has been shown that polycyclic aromatic hydrocarbons require metabolic activation before they can act as mutagens or carcinogens. This metabolic activation results from interaction with microsomal enzymes present in many body cells, yielding reactive epoxides which react with DNA and produce mutations in the count frame shift or participate in covalent bounding. While opinions differ regarding the relative role of these processes in mutagenesis, considerable evidence exists which links mutagenesis and carcinogenesis. Metabolites of the polycyclic aromatic hydrocarbons which are carcinogenic are usually mutagenic, which supports the hypothesis that damage to chromosomes plays an important role in carcinogenesis. These facts open the possibility to monitoring the spread of carcinogenic substances in the biosphere by relatively simple tests whose endpoint is mutagenesis.


Predicting toxicometric parameters on the basis of studying the concentration--time dependence.

A short-time exposure on the concentration--time relationship base, a classification of substances according to the degree of hazard and the program for assessing safety coefficients have been suggested in order to predict the basic toxicometric parameters (chronic exposure thresholds, maximum allowable concentrations, safety coefficients, and others).


Morbidity and mortality study of shale oil workers in the United States.

The study of the carcinogenic potential of domestic U. S. shale oil has increased significantly in importance because of the present energy problem and resulting research into alternative sources of fuel. With the increased scope of planned oil shale activity on the Colorado Plateau, it is important that an attempt be made to determine the health effects, if any, of occupational exposure to shale oil. This paper briefly reviews some past work of Soviet and British investigators concerning potential health hazards of shale oil. It reviews the results and conclusions of the 1952-1955 dermatological study of oil shale workers by the U. S. Public Health Service, and it discusses in detail the plans of a NIOSH morbidity and mortality study currently under way.


Cancer patterns in the oil shale area of the Estonian S.S.R.

Age-adjusted incidence rates of stomach, lung, and skin cancer among urban (1967-1972) and rural (1963-1972) population of four administrative districts in the Estonian S.S.R. have been presented. In the Kohtla-Järve district (oil shale area) there was an excess of stomach and lung cancer. High rates of stomach cancer in towns and boroughs of oil shale area may be explained by migration. A great proportion of migrants comes from regions, where incidence rates are 1.6-2.5. times higher than among estonians. Elevated levels of stomach cancer incidence in rural areas of Kohtla-Järva district remained unexplainable. In a retrospective cohort study of 2069 workers who had been exposed to oil shale products from 10 to 20 years an excess of skin cancer in females was found.


Processing use, and characterization of shale oil products.

Oil shale is a potential source of oil that will supplement conventional sources for oil as our needs for fossil fuels begin to exceed our supplies. The resource may be mined and processed on the surface or it may be processed in situ. An overview of the potential technologies and environmental issues is presented.


Influence of exposure mode on the toxicity of NO2.

Pollutant gases are subject to a variety of physical and chemical interactions within the atmosphere due to cyclic production and various meteorological influences. In consequence there is generally a diurnal concentration profile for NO2 which consists of peaks of short duration and irregular occurrence superimposed on a low background. Since this variation could play an important role in the toxic effect of NO2, the influences of various exposure modes was studied. Continuous and intermittent exposure studies were used to determine the relationship between biological response and length of exposure to various concentrations of NO2. As the concentration decreased, the slope of the regression line decreased. After adjusting for total differences in the product concentration x time, the response for the two exposure modes was essentially the same. When a constant concentration x time level was employed, a short-term exposure to a high concentration produced a greater effect than exposure to a lower concentration administered over a longer period. Using these curves, the relationship between level of effect, concentration, and time can be determined. Results of these studies indicated that the frequency and amplitude of short-term peaks are of significance even though the exposure is interrupted with periods of zero concentration of NO2.


Experimental study of the mechanism and indices of harmful effects of certain chemical substances on the central nervous system.

The task of the second stage of Soviet-American cooperation on the problem of environmental health science was to explain the question of the comparative sensitivity of methods used in both countries, as well as the indices of harmful effects for the same toxic substance (carbon disulfide), with the purpose of determining the most informative methods of assessing the influence of atmospheric pollutants on organisms. The application of neurophysiological research methods (recording total electrical activity of the cortex and cortical structures of the brain, studying amplitude-time characteristics of averaged evoked potentials of the optical cortex, investigating sensory and convulsive thresholds) has made it possible to explain the neurophysiological basis of the effect of carbon disulfide on the central nervous system-the perturbation of cortical inhibition processes and the increase of excitation in amygdalate structures, both of which play an important role in the fixation process of temporary connection. The compilation of data from neurophysiological and neurochemical investigations show that neurophysiological changes are associated primarily with a decrease in enzymic breakdown of free neuraminic acid. The study of the average evoked potentials in humans during exposure to carbon disulfide concentrations of 0.09 mg/m(3) revealed a tendency to decrease the short latent amplitude components and increase the long latent amplitude components of the averaged evoked potentials. The study of operant behavior in rats revealed a characteristic change in the instrumental alimentary reactions under long-term (3 months) exposure of carbon disulfide to a concentration of 16 mg/m(3). IN THIS MANNER, THE FOLLOWING WERE DEVELOPED IN EXPERIMENTS WITH ANIMALS AND RESEARCH ON HUMANS: indices of the harmful effects of neurotropic toxic substances, a change in operant behavior, a decrease in the amplitude of total electrical activity, a change in time-amplitude parameters of evoked potentials, and a decrease in post-discharge convulsion thresholds in the cortical-medial nucleus of the amygdala. Neurophysiological and neurochemical research methods have proven to be the most sensitive and informative of the methods used. These criteria and methods are recommended for determining threshold levels of various neurotropic toxic substances which pollute the atmosphere.


Experimental study of biological effects of leads and aluminum following oral administration.

A wide spectrum of the biological effects of lead and aluminum ions is noted during short-term and long-term oral administration to laboratory animals. The general toxic and gonadotoxic effects of these metals during a short-term experiment appeared to be identical, and the correlation of these effects was preserved during chronic experiments. Lead (0.03 mg/l.) and aluminum (0.5 mg/l.) concentrations in water may be dangerous to the health of the population, and hygienic standards are recommended for inclusion in the standard for drinking water quality.


Assessment of environmental factors affecting male fertility.

Exposure to drinking water containing as much as 500 ppm aluminum chloride for periods of 30, 60, and 90 days had no apparent effect on male reproductive processes. In an attempt to correlate enzyme activity with particular spermatogenic cell types, postnatal development of testicular enzymes was studied. Eight enzymes were selected: hyaluronidase (H), lactate dehydrogenase isoenzyme-X (LDH-X), dehydrogenases of sorbitol (SDH), alpha-glycerophosphate (GPDH), glucose-6-phosphate (G6PDH), malate (MDH), glyceraldehyde-3-phosphate (G3PDH), and isocitrate (ICDH). Enzyme specific activities in testicular homogenates were determined. Two types of enzyme developmental patterns were observed. One was represented by H, LDH-X, SDH, and GPDH; and the other by G6PDH, MDH, G3PDH, and ICDH. The former was characterized by a change in enzyme activities from low in newborn to high in adult while in the latter this pattern was reversed. The two complementary enzyme systems crossed each other at puberty. Prior to puberty, only spermatogonial cells are present; sperm differentiation initiated at puberty adds spermatocytes and spermatids to the testicular cell population. Male rats were exposed to borax in their diet for periods of 30 and 60 days. Concentrations of boron were 0, 500, 1000, and 2000 ppm. At the end of each experimental period, the specific activities of the selected enzymes were determined in the testis and prostate. Correlations of enzyme activity with testicular histology and androgen activities of the male accessory organs were sought. In addition, plasma FSH, LH, and testosterone levels were measured to assess pituitary-testicular interaction. Plasma and testicular boron concentrations were determined and a minimum boron concentration which induced germinal aplasia and male infertility was estimated. In both 30 and 60 day feeding studies, male rats receiving 500 ppm failed to demonstrate any significant adverse effects. In contrast, male rats receiving 100 and 2000 ppm boron displayed a significant loss of germinal elements, although most of the Leydig and Sertoli cells appeared normal. Testicular atrophy was associated with a decrease in seminiferous tubular diameter and a marked reduction of spermatocytes and spermatogenic cells. These morphologic alterations were associated with a concomitant reduction of H, SDH, and LDH-X specific activities. In contrast, the specific activities of G3PDH and MDH were significantly elevated above control. The increase in these enzyme activities can be attributed to the relative enrichment of spermatogonial cells during the loss of spermatocytes and spermiogenic cells. Boron-induced male germinal aplasia was also associated with significantly elevated plasma FSH while plasma LH and testosterone levels were not significantly altered. Plasma testosterone levels were unaltered. Male fertility studies demonstrated that at the 500 ppm boron level, fertility was unaffected. However, at 1000 and 2000 ppm boron, male fertility was significantly reduced. Most effects were reversible within 5 weeks. However, the male group receiving 2000 ppm boron for 60 days remained sterile. There was no dose-related decrease in litter size or fetal death in utero. Therefore, the boron-induced infertility was apparently not due to a dominant lethal effect but rather to germinal aplasia. Boron appears toxic to spermatogenic cells at testicular concentrations of 6-8 ppm.


System of accelerating methods of evaluating toxicity and hazardous properties of substances.

By studying a group of organophosphorus compounds (PhOC), system of methods for developing models of chronic intoxication was approved, the purpose of which was to establish safe levels of chemical pollutants in the water. The magnitudes of threshold doses (TD) and ineffective doses (MID) were obtained by using MACrv (maximum admissible concentrations of substances in the air of industrial plants) and TLV [indices of admissible levels of substances in the air of industrial plants (USA standards)]. In compiling estimated and experimentally established MAC for 21 substances, variations were recorded within the range of 2-10 times. Forecasting on the basis of ED50, Elim and other measures during 5-20 day experiments made it possible to estimate threshold and inactive doses of PhOC during chronic intoxication, as well as to determine a cumulative coefficient and distribute these compounds into two series, according to the degree of their hazard. This project made it possible to determine cumulative properties simultaneously and forecast the chronic toxicity of the PhOC group under investigation.


Some physical factors in toxicological assessment tests.

Many thousand organic compounds are in common use and new ones introduced daily. With many of these materials, little is known about their toxic hazard. For years scientists have been investigating the relation of structure and properties to biological activity. Among the factors relating to toxicity are bioaccumulation and persistence in the organism. In this study, the relation of partition coefficient and solubility to bioaccumulation of some organochlorine compounds was investigated as was also the reactivity of several organophosphates. The work adds confirmation to the relation of molecular parameters to penetration, accumulation, and persistence in toxic action.


Approaches to the formulation of standards for carcinogenic substances in the environment.

After having agreed that standards are necessary for carcinogens that cannot be completely eliminated from the environment, two exchange groups in the U.S.S.R.-U.S. Cooperative present their different approaches to the problem. The Russian groups has recommended a benzypyrene standard of 0.1 microgram/100m3 of atmospheric air over populated regions and gives its experimental basis and theoretical rationale in the first part of this joint paper. Lifetime experiments in adult rats over a wide range of dose levels permit the determination of a largest ineffective dose level with respect the theoretical time of first tumor as well as incidence. The standard is set by extrapolation based on body weight and uses a safety factor of 10 to account for the additional susceptibility in embryogenesis and childhood. The U. S. group presents a mathematical model of time-to-tumor occurrence which permits the prediction of population incidence and life span shortening from time-to-tumor data in animals or man. It assumes the distribution of mortality-corrected time to tumor is lognormal with the nth power of time inversely proportional to dose and with dose independence of the variability of the logarithm of time to tumor. The prediction is made by combining this distribution, fitted to the data, with population mortality tables. Both groups emphasize that substantial research efforts are necessary to improve the scientific basis for setting standards.


Combined exposure to ozone and nitrogen dioxide.

A study of rats acutely exposed to ozone (0.5--2.0 ppm) or nitrogen dioxide (2--20 ppm) for 2 hr and sacrificed immediately thereafter shows little similarity in the individual biochemical effects of these pollutants. No evidence of nitrogen dioxide-induced lipid peroxidation was observed. Of interest is the finding that inhalation of nitrogen dioxide increases the extent to which concanavalin A agglutinates alveolar macrophages while ozone has exactly the opposite effect.


Study of some biological indices of the state of the sympathoadrenaline system under the effect of polychlorocamphene.

The effect of exposure to different amounts of polychlorocamphene (toxaphene) on the level of cathecholamines (noradrenalin and adrenalin), their precursors (DOPA and dophamine), and a metabolite (vanillylmandelic acid) in tissues (adrenals, brain, heart) and daily urine in white male rats has been studied. It was established that the single administration of 120 mg/kg toxaphene (half the LD50) as well as 2.4 mg/kg (1/100  of LD50) for 1 and 3 months produced a disturbance of catecholamine metabolism. The absolute level of ratio of separate components of the sympathicoadrenalic system is unequally changed in tissues, the breakdown of catecholamines is increased, and the specificity of their excretion is destroyed.


Effect of toxaphene on pyruvic and lactic acid levels in the rat.

Rats were given a single dose of toxaphene (120 mg/kg equilavent to 1/2 LD50) and sacrificed at 1, 5, and 15 days. No alterations of levels of pyruvic or lactic acid in blood plasma were observed. In a second experiment, rats were given 2.4 mg/kg daily and sacrificed at 1, 3, and 6 months, and again no alterations of pyruvic or lactic acid levels were found. It is concluded that observed alterations of the activity of lactic acid dehydrogenase induced by toxaphene do not give rise to physiological changes in unstressed rats.


Frequency and amplitude analysis of the EMG during exercise on the bicycle ergometer.

The surface EMG was recorded from above the quadriceps muscle in 3 male subjects during bicycle ergometry at work loads between 20 and 100% of the VO2 max to measure the EMG amplitude (RMS) and frequency (assessed from the center frequency of the power spectra) during this type of work. During brief (3 min) bouts of work the RMS amplitude of the EMG was linearly related to the work load; the center frequency of the EMG power spectra was the same at all work loads examined. In contrast, during sustained bouts of work maintained for 80 min at 20 and 40% of the VO2 max, the RMS amplitude of the EMG remained constant while the center frequency initially increased for the first 20 min of work and then progressively decreased as the work continued. When work loads of 60, 80, and 100% of the VO2 max were sustained to fatigue, the RMS amplitude continually increased while the EMG frequency decreased from the beginning to the end of the work periods. The results of this study showed that the EMG is a complex waveform, being influenced not only by fatigue, but to even a larger extent in many cases, the temperature of the exercising muscles. Therefore, although muscular fatigue caused an increase in the RMS amplitude and decrease in the center frequency, the increase in muscle temperature associated with the work opposed these changes by causing a reduction in the RMS amplitude and an increase in the center frequency.


Muscular fatigue and rate of tension development.

The effects of long-term fatigue upon maximal force and peak rate of tension development (PRTD) (dF/dt max) are studied in man (elbow flexors), in the rat (pseudo-isolated gastrocnemius muscle) and in the frog (isolated sartorius muscle). The muscles are fatigued by voluntary anisometric anisotonic contractions against an elastic resistance in man, and by maximal tetanic contractions in the frog and the rat. In man, the excitation level of the muscle is controlled by the integrated surface EMG of the biceps brachii. In the animals, the muscles are stimulated by a neurostimulator. The PRTD and the maximal isometric force are measured during fatigue tests. In man, frog and rat, the maximal voluntary isometric torque or the maximal force and the PRTD decrease initially more or less rapidly according to the power developed during the fatigue process, and then less rapidly. The relationship between PRTD and maximal force is linear in the animals and curvilinear in man. The variations of maximal force and PRTD are discussed in relation to the level of excitation of the muscles and of the composition in different motor units types and their spatio-temporal recruitment. From a biomechanical point of view, it seems necessary to study the behavior of the series elastic component during the evolution of long term fatigue.


Optimal hematocrit for canine skeletal muscle during rhythmic isotonic exercise.

Contractile power, blood flow, O2-uptake, and O2-extraction during isotonic, rhythmic exercise were determined in the isolated canine gastrocnemius muscle during perfusion with blood with hematocrits between 0.21 and 0.81. The results obtained in 36 measurements on nine muscles showed that maximal O2-delivery to the muscle if found at hematocrits between 0.5 and 0.6. Both in the range of hemodilution, and in the range of extreme hemoconcentration, O2-delivery decreases significantly. O2-consumption and contractile power of the muscles are almost unaffected in the hematocrit range between 0.4 and 0.7; beyond and below this hematocrit range both parameters decrease. O2-extraction is virtually constant in the hematocrit range between 0.3 and 0.6, but increase both below and above these hematocrit levels. It is concluded that due to reduced vasodilatory reserve in working skeletal muscle compared to resting muscle the optimal hematocrit is shifted to higher values.


Plasma aldosterone, renin activity, and cortisol responses to heat exposure in sodium depleted and repeleted subjects.

The effect of 90-min heat exposure (46 degrees C, 35 mbar) on plasma aldosterone (PA) patterns was studied and the respective roles of plasma renin activity (PRA), adrenocorticotropin (ACTH), Na+ and K+ concentrations in the control of PA response were in investigated in eight subjects on a low sodium diet and in five subjects on a high sodium diet. In all subjects, transitory PA increases of varying importance were observed, which were not related to sweat losses (less than 1% bodyweight) or to rectal temperature rise. In sodium-repleted subjects, basal PA and PRA levels as well as heat-induced rises were low (mean PA peak level = 12.62 +/- 1.15 ng/100 ml). They were enhanced by sodium depletion and PA reached a mean peak level of 34.07 +/- 2.73 ng/100 ml. But, in both conditions, the heat-induced PA peaks were 3-times higher than the initial levels. PA correlated with PRA in all but one of the sodium-repleted subjects and in 6 of the 8 sodium-depleted subjects. ACTH release, as measured by plasma cortisol (PC) levels, occurred in those subjects who noted an increased feeling of annoyance and discomfort. Thus, PA correlated positively with PC in 4 sodium-depleted subjects. A high sodium intake improved heat-tolerance. Plasma K+ and Na+ concentrations were not significantly modified by exposure to heat. PA increases can occur without concomitant changes in PRA, PC, K+ or Na+, which suggests that an additional factor may play a role in aldosterone regulation during acute heat exposure.


Metabolic response to heavy physical exercise before and after a 3-month training period.

Twenty healthy athletes performed a heavy physical exercise before and after a controlled training period of 3 months. As a result of physical training there was a reduction in lactate concentration during and after exercise. Plasma free fatty acids and triglyceride levels were lower at rest as well as during and after exercise. Insulin concentrations decreased during exercise before the training period whereas they remained constant afterwards. The composition of individual free fatty acids changed in the same way during exercise before and after training: fatty acids with shorter hydrocarbon chains increased, those with longer chains decreased. Comparing the pattern of individual free fatty acids before and after training a higher percentage of saturated and a lower percentage of mono-unsaturated fatty acids was observed. It is concluded that changes in the plasma free fatty acid profile during heavy exercise reflect a preferential uptake and oxidation of certain individual free fatty acids. The significance of training-induced changes in the plasma free fatty acid pattern is discussed.


Biochemical changes in a 100 km run: free amino acids, urea, and creatinine.

Free amino acids, urea, and creatinine were analyzed in venous blood and urine of 11 trained (28--81 years old) male subjects before, immediately after, and 1 day after a 100 km running competition. The urinary excretion per minute of all amino acids was lowered after the contest. The renal clearance of creatinine was reduced from 116 to 60 ml/min and the clearance of most amino acids was reduced to a similar extent. However, for the amino acids with a resting clearance under 1 ml/min (x), a high relative clearance ratio (y in % of x) was seen post-exercise: y = -92.3 (log10 x) +23.1, r = -0.83, showing that their high reabsorption capacity had been impaired. Serum concentrations of most free amino acids, including the branched-chain amino acids and alanine, were reduced to 35--85% of the pre-race values. The sulfur amino acids were elevated either at the end of (cystine, to 180%) or 24 h after (methionine, to 155%) the race. Urea production increased by 44% while creatinine production tended to decrease. The production of 3-methylhistidine remained unchanged. These findings are compatible with a stimulation of gluconegenesis at the expense of the amino acid pool without induction of muscle protein catabolism.


Cathepsin D of rat spleen. Affinity purification and properties of two types of cathepsin D.

Two types of cathepsin D were purified from rat spleen by a rapid procedure involving an acid precipitation of tissue extract, affinity chromatography with pepstatin--Sepharose 4B and concanavalin-A--Sepharose 4B, and chromatography on Sephadex G-100 and DEAE-Sephacel. The purified major enzyme (85% of the cathepsin D activity after DEAE-Sephacel chromatography), termed cathepsin D-I, represented about a 1000-fold purification over the homogenate and about a 20% recovery. The purified minor enzyme (15%), termed cathepsin D-II, represented about a 900-fold purification and about a 3% recovery. Both enzymes showed four (pI: 4.2, 4.9, 6.1 and 6.5) and three (pI: 4.6, 5.6 and 5.8) multiple forms after isoelectric focusing, respectively. The purified enzymes appeared homogeneous on electrophoresis in polyacrylamide gel and had a molecular weight of about 44000. In sodium dodecylsulfate/polyacrylamide gel electrophoresis both enzymes showed a single protein band corresponding to a molecular weight of 44000. The enzymes had similar amino acid compositions except for serine, proline and methionine. Cathepsin D-I contained 6.6% carbohydrate, consisting of mannose, glucose, galactose, fucose and glucosamine in a ratio of 8:2:1:1:5 with a trace of sialic acid. The properties of purified enzymes were also compared.


Fatty-acid synthesis in lactating-goat mammary gland. 1. Medium-chain fatty-acid synthesis.

Tissue slices from lactating goat-mammary gland synthesized short (C4:0 and C6:0), medium (C8:0 and C10:0) and long-chain (C12:0 to C16:0) fatty acids in proportions similar to that found in goat milk fat. In contrast, the particle-free supernatant fraction and the purified fatty acid synthetase from this tissue synthesized predominantly short-chain and long-chain fatty acids. Terminating acyl-thioesterases of low molecular weight could not be detected in the particle-free supernatant. Addition of the microsomal fraction to the particle-free supernatant induced the synthesis of medium-chain fatty acids in proportions which were similar to those found in goat milk fat.


Fatty-acid synthesis in lactating-goat mammary gland. 2. Medium-chain fatty acid synthesis.

Addition of goat, rat, rabbit and cow mammary microsomal fraction to fatty acid synthetase of goat mammary gland induced C10 fatty acid synthesis. When the microsomal fractions from rat, rabbit and cow mammary gland were incubated with their respective fatty acid synthetases only the cow enzyme synthesized significant amounts of C10 compared to the purified fatty acid synthetases alone. The goat mammary microsomal fraction was not able to induce C10 synthesis by rat and rabbit mammary-gland fatty acid synthetase, but only by the goat and cow enzyme. Both goat and cow mammary-gland fatty acid synthetase have in contrast to the rabbit and rat enzymes the ability to hydrolyse medium-chain acyl-thioesters. We therefore suggest a novel mechanism for medium-chain fatty acid synthesis in lactating-goat mammary gland. This mechanism involves an activation of the medium-chain acyl-thioester hydrolase within the fatty acid synthetase of goat mammary gland by an unknown microsomal factor.


Characterization of the isoenzymes of pig-liver esterase. 1. Chemical Studies.

Three different subunits of highly purified pig liver esterase (EC 3.1.1.1) can be separated by analytical dodecyl sulfate electrophoresis, though their relative mobilities are very similar. The same subunit bands are obtained with microsomes, in which the esterases have been labeled with the specific active-site-directed inhibitor bis(4-nitro-[14C]phenyl)phosphate. The heterogeneity of the native trimeric enzyme is much more complex, as is demonstrated by isoelectric focussing and polyacrylamide gel electrophoresis. Fractions of esterase which were partially separated by preparative isoelectric focussing show differences in their subunit composition, their amino acid analyses, their tryptic peptide maps, and their C-terminal amino acids. From these experiments various features of the differing esterase subunits can be deduced. Based on the chemical results and on various experiments which did not indicate any secondary modification of the protein side-chains, the molecular basis of the esterase heterogeneity is discussed. We conclude that the native trimeric esterase is a mixture of numerous hybrids of at least three protein subunits with differing but closely related primary sequences. A comparison of the relative specificity of various preparations of pig liver microsomes indicates that genetic differences concerning the composition of liver esterase exist between individuals.


beta-Like globin RNA sequences in hemoglobin Lepore disease.

A Southern Italian patient homozygous for hemoglobin Lepore disease synthesizes approximately 3% Lepore delta beta-globin chains (relative to alpha chains) in the reticulocytes. Measurement of beta-like RNA sequences by hybridization to complementary DNA specific for beta-globin demonstrates a low level (1--2% relative to alpha sequences) of these sequences in cytoplasmic RNA from reticulocytes or spleen cells, suggesting that the Lepore gene is expressed into mRNA at a lower extent than normal alpha or beta genes; the comparison with the level of beta-like sequences found in nuclear RNA (6--8%) further supports this conclusion and indicates, in addition, that Lepore RNA might be degraded at a faster rate than normal. 2--3% beta-like sequences are found in nuclear RNA in three cases of homozygous beta0-thalassemia, setting the highest possible estimate for the delta-RNA level; this figure suggests that the 'delta-promoter'-dependent Lepore delta beta gene is somehow more actively expressed than the delta gene.


Cholesterol 7 alpha-hydroxylase in isolated rat liver cells.

1. The activity of cholesterol 7 alpha-hydroxylase found in the 10000 x g supernatant prepared from isolated rat liver cells was comparable to that found with microsomal fractions from whole liver. 2. The activity of cholesterol 7 alpha-hydroxylase from cells prepared from livers of rats fed the bile salt sequestering agent cholestyramine was 2--3 fold higher than the activity of this enzyme found in cells isolated from animals on a control diet. 3. On incubation of hepatocytes in a suitable medium at 37 degrees C, cholesterol 7 alpha-hydroxylase activity declined to about 50% of its original value after three hours despite the fact that the cells retained a high level of viability over 5--6 h as measured by various sensitive criteria. 4. The decrease in cholesterol 7 alpha-hydroxylase activity was observed whether cholestyramine was included in the diet or excluded from the diet of the animals used as sources of the liver cells. 5. The change in cholesterol 7 alpha-hydroxylase activity seen on incubation of the cells was not affected by including in the incubation medium additional nutrients such as amino acids, the glucocorticoid cortisol, phospholipid dispersions, or sodium taurocholate. 6. Changing the incubation medium in which the cells were suspended at regular intervals during the three-hour experiments failed to prevent this decline in the cholesterol 7 alpha-hydroxylase activity during the incubation of these cells. 7. Although isolated liver cells have been shown to lose glutathione on incubation, addition of physiological levels of this compound did not prevent the decline in cholesterol 7 alpha-hydroxylase activity. 8. Cycloheximide addition to the incubation medium accelerated the decrease in cholesterol 7 alpha-hydroxylase activity. This suggests that some protein synthesis associated with cholesterol 7 alpha-hydroxylase activity occurs during the incubation and inhibition of such protein synthesis accelerated the decrease in this enzyme activity. 9. The cytochrome P-450 content of the 10000 x g supernatant prepared from hepatocytes declined slowly to about 65% of its original value after four hours of incubation at 37 degrees C. This decline in the 10000 x g supernatant cytochrome P-450 content may partly explain the observed loss of cholesterol 7 alpha-hydroxylase activity during incubations in vitro. 10. Isolated hepatocytes rapidly take up radioactively labelled sodium cholate. Subsequent excretion of the radioactivity was also very rapid even in the presence of large amounts of this bile salt in the medium.


Actin in mammalian lens.

In this paper evidence is provided that one of the protein components of the water-soluble fraction of the calf lens binds specifically to deoxyribonuclease I (DNAse I). On the basis of this property, the polypeptide could be purified by applying DNAse I affinity chromatography. Concomitantly a protein of Mr55000 and a rather large amount of alpha-crystallin copurify with this polypeptide, which has a molecular weight of 42000. Highly purified 42000-Mr protein was also obtained by extraction of the water-insoluble fraction of the calf lens with 2-([tris(hydroxymethyl)methyl]amino) ethanesulfonic acid followed by gel filtration. Amino acid analyses, peptide mapping and electron microscopy show that the protein obtained from both lens fractions is identical to non-muscle actin. Furthermore the amino acid composition of the 55000-Mr protein is identical to hog stomach skeletin and very similar to calf brain desmin.


The molecular size and shape of the Folch-Pi apoprotein in aqueous and organic solvents.

In 1% acetic acid, sedimentation velocity measurements and equilibrium ultracentrifuge experiments demonstrate that the Folch-Pi apoprotein is not monodisperse. The weight-average molecular weight calculated from ultracentrifuge experiments and combining sedimentation coefficient and viscosity measurements, ranged from 64000 to 80000. The intrinsic viscosity value suggests an asymetric shape for the apoprotein if a low value of hydration is considered. In dioxan/1% acetic acid (2:3, v/v) a smaller sedimentation coefficient was found, the intrinsic viscosity value remaining identical to that in 4% acetic acid. In pure 2-chloroethanol, light-scattering experiments led to a molecular weight of 165000 indicating that even in this solvent the protein is not monomeric. Intrinsic viscosity and light scattering measurements on the one hand, primary sequence on the other hand (six proline residues per monomer of Mr 23500) suggest that the molecule in 2-chloroethanol may consist of rod-like segments with flexible junctions.


Inactivation and disassembly of the pyruvate dehydrogenase multienzyme complex from bovine kidney by limited proteolysis with an enzyme from rat liver.

Mammalian pyruvate dehydrogenase multienzyme complex is inactivated when treated with a leupeptin-sensitive enzyme (termed 'inactivase') obtained from rat liver lysosomes. However, the inactivation of the overall reaction does not affect any of the component activities of the enzyme complex. By several methods it is demonstrated that treatment with the inactivase provokes the disassembly of the complex into its constituent enzyme components which, though being enzymatically active when assayed separately, are unable to catalyze the coordinated reaction sequence of pyruvate oxidation. The dissociation occurs as a consequence of limited proteolysis of the lipoate acetyltransferase core of the multienzyme complex. Isolated nicked acetyltransferase retains its complete enzymatic activity and behaves as a high-molecular-weight aggregate. The lipoamide dehydrogenase and pyruvate dehydrogenase components, however, are not cleaved by the inactivase.


Rearrangements in the course of ribonuclease hydrolysis of pre-messenger ribonucleoproteins. A warning.

A study of the action of ribonuclease on 30--50-S monoparticles prepared from pre-messenger ribonucleoprotein (pre-mRNA . protein) was started in order to elucidate the structure of monoparticles. A ribonucleoprotein complex containing mostly 30000--38000-Mr proteins of pI 7--9 (alpha class) persisted under conditions where other proteins (23000--110000 Mr, pI 5--8.5, beta class) were relased. An unexpected increase of sedimentation coefficient accompanied the formation of the ribonucleoprotein complex. The extent of increase varied with the initial size of the monoparticles, reaching 45% for 30-S monoparticles. The ribonucleoprotein complexes designated here as 40--45-S alpha-ribonucleoproteins were more homogeneous in size than the original monoparticles. Electron microscopic examination showed that the sedimentation shift corresponded to an increase of the actual size of the particles, not to flattening or change of shape. Therefore, the 40--45-S alpha-ribonucleoprotein is not a pre-existing unit of pre-mRNA . protein but arises from specific rearrangements probably between small alpha ribonucleoproteins formed by fragmentation of monoparticles. In addition to the 40--45-S alpha-ribonucleoproteins, large protein aggregates corresponding to 15% of the monoparticle proteins were formed upon ribonuclease hydrolysis. Their major proteins were neutral, suggesting that the aggregates might be precipitates of proteins at pH close to the pI. Ribonuclease being a widespread cellular enzyme, partial rearrangements may occur during preparation and handling of pre-mRNA . protein. It is particularly crucial to remark that the 40--45-S alpha-ribonucleoprotein which does not pre-exist might be mistaken for a pre-mRNA . protein unit.


Involvement of calcium in the inhibition by insulin of the glucagon-stimulated adenylate-cyclase activity.

1. The inhibitory effect of adenosine on the glucagon-stimulated adenylate cyclase activity of liver plasma membranes, prepared from PVG/c rats, was potentiated by insulin. In the presence of EGTA, such potentiating effect of insulin was lost. 2. Calcium (10 microM) potentiated the inhibitory effects of both adenosine and insulin on the glucagon-stimulated cyclase activity. The synergestic effect of calcium + insulin required the presence of adenosine as judged from the use of adenosine deaminase. 3. Insulin had no significant inhibitory effect on the glucagon-stimulated cyclase activity of liver plasma membranes, prepared from young Wistar rats, unless both adenosine (50 microM) and calcium (10 microM) were added externally. 4. Results demonstrate an interaction of calcium and insulin at membrane level that, in the presence of adenosine, results in the inhibition of the glucagon-stimulated adenylate cyclase activity.


Rectal bladder in the treatment of bladder exstrophy.

Satisfactory results were obtained in 25 patients with bladder exstrophy treated by the Heitz-Boyer-Hovelacque operation.


Endoscopic urethrotomy in the treatment of urethral stenosis.

After reviewing  the different therapeutic methods for urethral stenosis in the male, the results obtained with Sachse's urethrotomoscope (UTC) was studied in 25 patients checked within a period of between 6 and 28 months. Patients were judged cured when they maintained normal clinical, radiological and urodynamic parameters without treatment; 75% of the patients could be included in that series. Urethral stenosis (US) is a last stage common to distinct pathological causes (congenital, infectious, iatrogenic, traumatic), and lesions, together with their anatomicopathological consequences, merit special study because they contribute to bring valuable data to therapy.


Surgical management of renal staghorn calculi by selective hypothermic perfusion.

18 patients with unilateral staghorn calculi managed by selective hypothermic perfusion are presented and the results reported. The procedure proved to be simple, safe and effective in the management of most staghorn calculi.


Fracture of the penis: surgical management.

Two cases of fracture of the penis are reported. Early surgical repair of laceration of the corpus cavernosum brought about excellent results.


Etiological aspects and interest of early surgical management of priapism.

12 patients have been treated for priapism between March 1973 and September 1977. Etiologic conditions have been found 9 times, leaving only 3 idiopathic priapisms. Treatment of choice consisted of 8 saphenocavernous shunts, achieving detumescence in 7 cases and preserving sexual potency in 5. The precocity of operation seems of no interest to priapism itself but is mandatory to prevent secondary impotence.


Vaginocystography in vesicovaginal fistulae.

The importance of vaginocystography as an additional tool to excretory urography and cystoscopy in assessment of vesicovaginal fistulae is emphasized. A simple technique applicable even to large and multiple fistulae or a capacious vagina is described and discussed.


Anterior vaginal repair, cause of troublesome voiding disorders?

Clinical experience and urodynamic observations in 85 female patients with voiding disorders after anterior vaginal repair are presented. Iatrogenic or persistent urinary stress incontinence (72%), irritable trigone syndrome (48%), bladder outlet obstruction (40%), unstable bladder (25%) and recurrent cystitis (23.5%) were the most frequent findings. Also, 5 cases of urogenital fistula and 2 cases of loss of a great part of the urethra were noted. Attempts to cure these complications with different pharmacologic agents and/or surgical methods were often disappointing.


Calcitonin load in absorptive hypercalciuria type I.

The persistence of hypercalciuria (HCU), despite long-lasting calcium restriction in the diet in patients with absorptive HCU type I gives evidence of an additional endogenous source of calcium contributing to the pathogenesis of this disorder. The role of calcium mobilization from the bone is documented by the effective suppression of enhanced calcium mobilization from the bone, by means of calcitonin load in 5 patients with absorptive HCU type I and comparison with 7 normal controls.


Total pelvic arterial embolization in a case of massive vesical and vaginal bleeding by pelvis carcinomatosis.

A case of massive vesical and vaginal bleeding due to a primitive uterine cancer that relapsed hemorragically after bilateral hypogastric embolization and required an additional embolization of all arterial sources supplying the tumor is reported.


Renal arterial thrombosis after the contralateral removal of a pelvic kidney.

In a 19-year-old female a pelvic kidney, on the left side, was removed because of recurrent urinary tract infections, severe abdominal complaints and a pathological isotope-nephrography. Following nephrectomy a severe uremia with cerebral edema and pneumonia developed based on a medial necrosis of the artery of the right kidney. After surgical correction the function of the right solitary kidney returned to normal.


Spontaneous rupture of renal pelvis during postobstructive diuresis.

A case of spontaneous rupture of the renal pelvis during postobstructive diuresis following spontaneous relief of anuria in a patient with postpyelolithotomy retroperitoneal fibrosis, is described. The unusual etiopathological setting which predisposed to the occurrence of such a rare phenomenon and its treatment implications are discussed.


Unilateral emphysematous pyelonephritis.

A case of unilateral emphysematous pyelonephritis is presented in a patient with uncontrolled diabetes mellitus. The diagnosis was established from the presence of gas in the renal parenchyma, the pelvicalyceal system and the ureter. The patient was treated with a prolonged course of antibiotics and the function of the left kidney returned to normal.


Transitional cell carcinoma arising from bladder left behind.

A case of transitional cell carcinoma arising from a bladder which was left behind for more than 24 years without pyocystis syndrome is described. A search in the literature revealed 10 cases of defunctionalized bladder that developed tumors over a rather short latent period ranging from 3 months to 7 years, and mostly with evidence of severe bladder infection.


Renal cystic diseases in children--classification.

This paper reports on the classification of renal cystic diseases in children. Three main types are observed: dysplasic, familial and others, the latter including the medullary sponge kidney. This paper also aims at settling some terminology problems.


Endometriosis of the ureter.

Endometriosis of the ureter is an exceptional cause of ureteral obstruction. Pathogenesis and clinical picture are demonstrated on the basis of 2 cases, giving an example for the spread of endometrial tissue via the lymphatics. It is emphasized that young women should have a gynecological examination in case of pelvic ureteral obstruction. Final diagnosis of the isolate ureteral endometriosis can only be made by histological examination. Therapy is usually surgical followed by hormonal treatment. The routine use of excretory urograms in women suffering from endometriosis should prevent urological complications.


Antireflux in patients with neurogenic bladder.

The results of ureteral reimplantation in 8 neurogenic bladders with a high outflow resistance and severe trabeculation are presented. Operation was successful in all cases. The conditions for a successful intervention in these cases are: (1) previous or simultaneous treatment of the high outflow resistance: intermittent catheterization was found to be an excellent method for this purpose, and (2) the submucosal tunnel should be created preferably upon the trigone which is the only place free of trabeculation. High outflow resistance and severe trabeculation should no longer be considered as contraindications for antireflux surgery in the neurogenic bladder.


Antiandrogens in the treatment of prostatic cancer.

Since prostatic carcionma is hormone dependent, treatment of this tumor has been carried out in this department over the last 10 years employing antiandrogens, particularly cyproterone acetate (CPA), associated in some cases with orchiectomy. Of 500 patients thus treated, the author reports on 236 patients with a 5-year follow-up and 184 with a 7-year follow-up. Of these, 126 (53.4%) had not received hormone treatment whereas 110 (46.6%) had been treated with estrogens. The mean survival rate was 64.4% at 5 years and 56.3% at 7 years in these patients and 51 and 43%, respectively, in the estrogen-treated patients. The author emphasizes that not only is CPA of great value in the treatment of prostatic carcinoma, but it is also useful in determining the hormone dependency of the tumor which is indispensable before proceeding with hormone therapy.


Angiographic features of xanthogranulomatous pyelonephritis.

Preoperative diagnosis of xanthogranulomatous pyelonephritis (XGP) is possible in numerous cases by renal angiography, thus permitting the differentiation of this disease from renal adenocarcinoma. Angiographic features are reviewed in patients with proved XGP. The most useful findings are: (1) presence of hypervascularised areas; (2) dilated renal capsular and perforating arteries, and (3) heterogenous aspect of the kidney during the nephrographic period.


Histological grading of transitional cell tumours of the bladder. Value of histological grading (WHO) in prognosis.

Mortality among 139 patients with transitional cell tumour of the bladder was studied. Tumours were reevaluated according to the grading system recommended by WHO. The absolute 5-year survival of histologically benign papilloma cases was 68%, of grade I carcinoma cases 64%, of grade II carcinoma cases 42% and of grade III carcinoma patients 34%. Clinical staging (UICC), however, would have been more effective than histological grading (WHO) for prognostic purposes. 3 of the 14 patients with histologically benign papilloma in this study developed grade I carcinoma during follow-up periods of between 4.5 and 24 years. Following radical treatment all recurrences were papillomas. The study suggests that histological grading should be used to complement clinical staging in prognosis and that with half-yearly check-ups and elimination of any tumours thus detected, patients with papilloma rarely develop carcinomas of higher grade than grade I.


Renal cancer steroid receptors: biochemical basis for endocrine therapy.

Estradiol receptor (ER) and progesterone receptor (PR), found in experimental renal cancer as well as in normal human kidney and in human renal cell carcinoma (RCC), have been measured in 27 RCCs from patients submitted to surgery and endocrine therapy in an attempt to predict the response to progestational therapy. Of these 27 tumors 59% were positive for ER and 59% for PR; 37% were positive and 19% negative for both ER and PR. The follow-up of 23 patients showed that progestational therapy, started in 18 patients, has given favorable results in 14 patients and negative results in 3 patients with ER-PR- renal cancer. Antiestrogenic therapy, started soon after nephrectomy in 1 patient with ER+PR- renal cancer and lung metastases, failed since the patient died 8 months after surgery.


Relationship between the severity of renal stone disease and urine composition.

The biochemical findings in urine from 62 male and 20 female consecutive patients with renal stone disease were studied in relation to the size of concrements and the estimated rate of stone formation. There appeared to be good agreement between urine composition and stone history. Biochemical grouping of the patients resulted in different distributions in the different groups of stone-formers. The quotients calcium/magnesium (k1) and calcium X oxalate/magnesium X creatinine (k3) appeared to reflect the severity of stone disease and seemed to provide a rational approach to the evaluation of patients with urolithiasis.


Diphallia with a normal and a blind-ending urethra.

A 65-year-old male with incomplete double penis is reported. He has a duplicated glans on a single shaft. Both glans each have an urethra surrounded by a corpora spongiosum. The right urethra drained a normal bladder and the left urethra vanishes near the seminal colliculus.


A novel interaction involving a polypeptide chain (P33) in covalent linkage with IgM on the surface of a Burkitt lymphoma cell line (Daudi).

The surface IgM of Daudi Burkitt lymphoma cells has been shown to consist of mu chains and kappa chains covalently linked, by disulfide bonding, to a novel polypeptide chain of approximate molecular weight 33,000. This novel polypeptide chain (P33) is similar in several properties to the heavy chain of the Ia antigen: glycoprotein nature; apparent molecular weight; isoelectric behavior and cysteine content. The linkage of P33 to surface immunoglobulin has not been observed with any other human lymphoma or lymphoblastoid cell lines.


Deficiency of high-affinity anti-beta-D-galactosidase antibodies in selected low immune responder mice.

Amount and affinity of anti-beta-D-galactosidase-activating antibodies (AAb) were studied in two lines of mice obtained by selective breeding for antibody response to heterologous erythrocytes. These lines, referred to as high (H) and low (L) lines, differ also in their responses to many antigens. Concerning AAb amounts, the maximal titer in H mice is higher than in L mice. However, the AAb levels in H mice decreased with increasing immunizing doses and became lower than in L mice for the highest dose. This fact can be explained in terms of intramolecular competition or suppression. Whereas the usual maturation pattern was observed in H mice, no AAb of high affinity were found in L mice, even after a minimal immunizing dose. At any dose tested, no maturation of AAb occurred until three months after immunization. This deficiency may be ascribed to B lymphocyte or macrophage modifications. A correlation between the deficiency of high-affinity AAb in L mice and their genetically induced low antibody responsiveness cannot be proved.


Effects of irradiation and storage on granulocytes harvested by continuous-flow centrifugation.

Five normal subjects were subjected to leukapheresis by continuous-flow-centrifugation (CFC) in the Aminco Celltrifuge. Granulocyte functional capacities were evaluated on the venous blood samples drawn before apheresis and on the cell-rich plasma collected by CFC, immediately after collection and after short-term storage at 4 degrees C with or without previous irradiation (1500 rad, 50 rad/min). The CFC technique has been shown to provide cells without functional damage. Irradiation did not appear to influence granulocyte function, as evaluated by in vitro studies. The data demonstrate that granulocytes maintain, even after irradiation, functional activities similar to those found immediately after collection for up to 24 hours of storage at 4 degrees C and exhibit only a moderate loss of function after 48 h. Chemotaxis appears to be the most sensitive detector of cellular damage of stored granulocytes, either irradiated or non-irradiated; this technique may be the most useful for assessment of granulocyte function before transfusion.


Suppressive effect of interferon on erythroid cell proliferation.

The effect of interferon on mouse and human in vitro erythropoiesis was investigated using the mouse marrow CFU-E and the human blood BFU-E systems, respectively. Homologous interferons were found to have a marked inhibitory effect on mouse CFU-E and human BFU-E proliferation. This inhibitory effect was dose related and independent of the erythropoietin concentration used. The effective concentration of human interferon was within the range observed in humans following viral infections. It is suggested that interferon may play a role in the mechanism of the acute erythroblastopenic crisis observed at times in patients with chronic anemia following viral infections.


Stimulation by isoproterenol of erythropoiesis in cultures of dispersed cells of the primitive-streak chick blastodisc.

Low concentrations of isoproterenol stimulated proliferation of precursors of erythroid cells in cultures of cells prepared from the developing chick blastodisc at the stage of the primitive streak. Propranolol blocked this stimulatory action but had no effect upon erythropoiesis in the absence of isoproterenol.


Mononuclear cell infiltration of the aortic intima in domestic swine.

The preparation of thick endothelial "häutchen" from microscopically lipid-free areas of the thoracic and abdominal aorta of 22 domestic pigs proved that there is a surprisingly frequent penetration of mononuclear blood cells into the subendothelial space. They are deposited on the intima in a diffuse or focal distribution as dense epi-, inter- and subendothelial cell infiltrates.


Encephalitis congenita symptomatica toxica in experimental conditions.

The object of the study was the cerebral cortex of newborn rat. Tissue samples for examination were collected from the 2nd to the 8th hour after birth. Experimental material was the tissue of control animals and newborns whose mothers had been treated with both ethanol and pyrazole throughout gestation, and also with either ethanol or pyrazole alone. Ethanol and pyrazole were administered by gastric tube, ethanol at doses of 8.0 g/kg body weight, pyrazole at doses of 36 mg/kg body weight. The results indicate that ethanol ingested by the mother during gestation inhibits cell maturation in the cerebral cortex, whereas the combined administration of ethanol and pyrazole produces a highly toxic action. Its morphological exponent are symptoms which support the diagnosis of encephalitis congenita symptomatica toxica.


Features and distribution of intracerebrally injected peritoneal macrophages.

Radioactively labeled macrophages were injected intracerebrally in order to acquire additional criteria for the identity of certain intracerebral cell types with cells of the monocyte-macrophage series. The intracerebral distribution of the labeled cells, their reactive ability following silver impregnation, and the formation of processes were considered as indications for ameboid motility. The localization, reactive ability, and structure of the cells were similar to that found in cells inside the brain which are considered to be monocyte derivatives, i.e., intraventricular cells such as epiplexus cells and supraependymal cells, progressive microglia, free subarachnoidal cells, and perivascular cells of intracerebral vessels. A survival time of 2 months was assumed for the cells since isolated, intracerebrally administered, peritoneal macrophages can still be demonstrated inside the subarachnoid space 2 months after the injection.


Acute and subchronic kidney injuries in mice induced by diphenylamine (DPA).

Adult and female mice were fed with diphenylamine by oral gavage. Mice of both sexes showed up with kidney injuries involving tubuli and some glomeruli. RE-cells in livers of both sexes were activated with content of yellowish-brown pigment.


Organophosphate pesticide DDVP-induced alterations in the rat cerebellum and spinal cord -- an electron microscopic study.

DDVP is an organophosphate pesticide whose neurotoxicity, in the form of cholinesterase inhbition, is well-known. Rats, weighing 200-225 g were given intraperitoneal injections of 3 mg/kg. DDVP daily for 10 days. Following perfusion-fixation, ultrathin sections of the cerebellum and spinal cord were examined with an electron microscope. A large number of electron-dense bodies exhibiting electron-lucid vacuoles were discernible in the perikarya of cerebellar neurons. Aggregations of mitochondria were also seen. Myelin-figures in dendrites and axons of the spinal cord were detected. Evidence of oedema was evident in the spinal cord.


Cytogenetic properties of Chinese hamster V79-E cells: G-banding, C-banding, nucleolar organizer regions, and sister chromatid exchanges.

A line of the Chinese hamster V79 strain, denominated as V79-E, is cytogenetically characterized. It has a modal chromosome number of 22. Chromosome morphology, G- and C-banding reveal strong differences from the normal complement of the Chinese hamster presumably caused by rearrangements of chromosome segments during the past 20 years of in vitro culture. 4 chromosomes possess terminal nucleolar organizer regions. Spontaneous sister chromatid exchanges occur with a frequency of 0.38 sister chromatid exchanges per chromosome.


Insensitivity of the ferritin iron core to heat treatment.

To test whether the reactivity of ferritin iron is affected by the heat treatment used in ferritin isolation, we prepared ferritin from the same horse spleen with or without heating. Both samples exhibited similar reactivity upon reduction or chelation of iron.


Effects of thyroidectomy on monoamine oxidase activities toward tyramine and serotonin in the circumventricular nuclei of the rat.

Following thyroidectomy, monoamine oxidase (MAO) activities toward tyramine decreased significantly by 20% in the nucleus periventricularis and the nucleus arcuatus among the 3 hypothalamic nuclei of the rat, while MAO activity toward serotonin decreased significantly by 10% only in the nucleus periventricularis. It is suggested that thyroidectomy induced selective changes on the multiple forms of MAO in the discrete circumventricular nuclei.


Tissue ascorbic acid and a liver dehydroascorbatase in guinea-pigs.

The extraction, partial purification and assay of a dehydroascorbatase from guinea-pig liver is described. There was no evidence that changes in dehydroascorbatase activity could account for the modified tissue ascorbic acid concentrations associated with aging or with the ingestion of fluoride, flavonoids or anthocyanin material.


Interstrain variation of murine arylsulfatase C.

A method has been developed for the assay of arylsulfatase C in tissue extracts containing arylsulfatases A and B. Significant variation of enzyme activity was observed among 26 inbred murine strains. Activity differences were apparent at all stages evaluated between 1 and 70 days postnatal age. Arylsulfatase C from representative high- and low-activity strains exhibited similar Michaelis constants, temperature optima, pH optima, thermostabilities and inhibitor profiles.


Chemical characterization of human urine albumin in proteinuria.

From the urine of a patient with proteinuria, the albumin protein component was isolated and compared with human serum albumin. By comparing the amino acid composition of the original proteins and their large cyanogen bromide fragments, peptide maps and N-terminal sequences of 33 amino acid residues, the identity of both proteins was shown.


Isolation of pathogenic treponemes from hare.

A presumably new species of pathogenic treponemes was isolated from a lesion on the male organs of hare (Lepus sp.) and the scrotum of a rabbit (Oryctolagus sp.) was infected with this treponeme. Lesion developed on the scrotum after a 110-day incubation.


On the inhibitory effect of 2-amino-4,6-dichloropyrimidine on growth of vaccinia virus.

2-Amino-4,6-dichloropyrimidine prevents maturation of Vaccinia virus. Proteins synthesized in the presence of the drug are not assembled into virions.


The fasciolicidal activity of a halogenated benzenesulfonanilide.

Halogenated benzenesulfonanilides have potent fasciolicidal activity. The efficacy of 1 such compound in mice, sheep, and cattle is reported.


Cytoplasmic contaminants in Triton X-100 washed rat liver nuclei - a possible way of further purification.

The presence of cytoplasmic contaminants is demonstrated in preparations of rat liver nuclei, even after washing with Triton X-100. They can be removed by incubation at 37 degrees C in a medium of low-salt concentration.


Penetration and interaction with haemoglobin of corynebacteria-like microorganisms into erythrocytes in vitro.

Following 24 h incubation of normal blood in the presence of the microorganism, the evolution of cell wall deficient forms within the erythrocytes and a process of oxidation of the haemoglobin may be observed.


A specific GT1 ganglioside-luteinizing hormone interaction induces conductance changes in lipid bilayers.

A specific interaction was demonstrated between GT1 gangliosides incorporated in bilayer membranes and luteinizing hormone. This interaction would allow the penetration of a hormone subunit in the membrane. The results are discussed in terms of adenylate cyclase activation.


Innervation by W-type retinal ganglion cells of superior colliculus neurons projecting to pulvinar nuclei in cats.

Neurons of the cat superior colliculus (SC) sending their axons to the pulvinar nuclei were identified electrophysiologically as the ones responding antidromically to electrical stimulation of the pulvinar nuclei. They were located in the superficial layers of SC and found to be innervated by axons of W-type ganglion cells of the retina.


Responses to stimulation of the peripheral end of the right splanchnic nerve in the conscious calf.

The ratio at which adrenaline and noradrenaline are released from the adrenal medulla in response to stimulation of the splanchnic nerve has been established in the conscious calf. The proportion of adrenaline:noradrenaline was closely similar to that in which the 2 amines are stored in the gland and released in response to other stimuli in conscious, but not anesthetized, calves.


Reduced deformability of erythrocytes exposed to hypercapnia.

The effect of hypercapnia on the deformability of erythrocytes was studied by means of a nuclepore membrane filter method. A decrement of the deformability by 20--40% was observed when PCO2 was increased from 50 mm Hg to 200 mm Hg, accompanied with an increment of 5% in hematocrit value.


Monolayer cultures of perikarya isolated from postnatal rat cerebellum.

Viable cerebellar perikarya of mixed cell type obtained from 7--9-day-old rats were maintained in monolayer cutlure for up to 12 days. During this time extensive neurite formation and outgrowth occurred. The large majority of the cells developing in culture were tentatively identified as granule neurons. This identification was based on the large number isolated from the starting tissue, and the cells' general morphological features in culture such as perikaryal and nuclear size, the bipolar nature of neurite extension, and their migratory behaviour.


Unexpected features of the interaction between individual primary afferents and spinal motoneurones.

Simultaneous intracellular recording from spinal motoneurone and dorsal root fibres afferent to it in the isolated amphibian cord revealed a specific correlation between the slow spontaneous depolarizing activity in motoneurones and primary afferents.


Spontaneous miniature potentials in primary afferent fibres.

Intracellular recording from primary afferent fibres of the isolated frog spinal cord revealed the existence of spontaneous synaptic activity, related probably to the firing of presynaptic inhibitory fibres.


High K+-induced release of somatostatin from the cortical preparation of rat brain.

Release of endogenous somatostatin (SRIF) from the rat cerebral cortical slices incubated in Krebs-bicarbonate buffer was increased from the basal rate of 3.4 +/- 0.6% of the total SRIF content in 15 min at [K+]o = 5.6 mM, to 13.1 +/- 1.6% upon raising the [K+]o to 56.6 mM. The high-K+ evoked SRIF release was absent when Ca++ in the medium was replaced by Mn++. The isolated synaptosomes from rat cerebral cortex contain 13.2 +/- 3.1 ng SRIF/mg protein compared to 0.33 +/- 0.01 ng/mg protein in the cortical tissue as a whole, suggesting that nerve terminals are the main source of the peptide released upon membrane depolarization.


Effects of D-alpha-aminoadipate on physiologically evoked responses of cat dorsal horn neurones.

Microelectrophoretic administration of D-alpha-aminoadipate reversibly reduced excitatory responses of cat dorsal horn neurones evoked by iontophoretic glutamate and non-noxious peripheral stimuli but did not influence similar responses evoked by noxious peripheral stimuli or iontophoretic substance P.


Stimulus-response function at several levels of background luminance, in the cat visual areas 17 and 18.

Stimulus-response curves of simple cells of the visual cortex were obtained by using 500-msec stationary stimuli. Background influence on single unit responses was studied. The contrast sensitivity of simple cells increases as a function of background luminance. The resolution power of these cortical cells for detecting differences in stimulus contrast decreases at background levels above 0.09 cd/m2.


Effects of hypothalamic injections of 5,6-dihydroxytryptamine on thermoregulation in rats.

5,6-Dihydroxytryptamine, a serotonin depletor, infused directly into the anterior hypothalamus of rat's brain, produced an increase in both heat production and heat loss (as indicated by changes in peripheral circulation) at temperatures of 8, 15 and 22 degrees C. The rectal temperature of these treated rats remained constant.


Changes in rat erythrocyte membrane induced by delta 1-tetrahydrocannabinol, scanning electron microscope study.

Although some biochemical dose-dependent effects are revealed in erythrocytes exposed to delta 1-tetrahydrocannabinol (THC) already at concentrations well below 10 microM, marked morphological changes of the erythrocyte membrane become evident, by scanning electron microscopy, only at THC concentrations beyond 15 microM. These observations provide evidence additional to previous chemical and physical studies, in which 15 microM is found to be a critical concentration with respect to the effects of TCH on erythrocyte membrane.


Electrophysiological actions of chlorimipramine on guinea-pig ventricular fibres.

Chlorimipramine (CMI, 1 x 10(-5)M to 7 X 10(-5)M) decreased the amplitude, overshoot and rate of rise of ventricular action potentials and abolished the Ca-mediated action potentials elicited in guinea-pig papillary muscles. These results indicates that CMI inhibits the rise in sodium and calcium conductances during the cardiac action potential.


Effect of ethanol on levels of isoniazid, sulfanilamide and sulfapyridin in mouse blood.

The effect of ethanol of blood levels of free and conjugated sulfonamides (sulfanilamide and sulfapyridin) and isoniazid was investigated in mice. Ethanol (1.5 and 4 mg/g i.v.) enhanced the amount of conjugated isoniazid without affecting the total amount of isoniazid in blood, and tended to raise the total amount of the sulfonamides.


Pharmacological studies of a new analgesic, dl-erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride, in experimental animals.

dl-Erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride showed orally a definite analgesic activity, without producing the significant morphine-like physical dependence liability, and its analgesic potency was about a half that of codeine and far superior to aminopyrine in experimental animals.


Gill lesions in Cichlid fishes after intoxication with the insecticide Fenthion.

The toxic effects of Fenthion on the gills of Cichlid fishes were investigated. In Herotilapia multispinosa hyperplasia and separation of the respiratory epithelium, lamellar telangiectasis and thrombosis occurred. The lamellar epithelium of surviving fish regenerated in all cases. In Tilapia leucosticta no telangiectasis was found, but all the secondary lamellae were fused due to the severe hyperplasia of the gill epithelium.


The effects of physostigmine on the oxygen uptake in rat brain tissue.

Physostigmine in a dose of 0.1 mg/kg i.v. expressly stimulated the oxygen uptake in the rat cerebral cortex. This effect was blocked by propranolol and seems be mediated by catecholamines. Since atropine also antagonized the stimulant effect of physostigmine, it appears that the action of physostigmine is primarily cholinergic and that the adrenergic effect is a secondary phenomenon. The higher dose of physostigmine (0.4 mg/kg i.v.) caused a depression of rat brain oxygen uptake.


Effect of dichloromethane on the sciatic motor conduction velocity of rats.

There is a correlation between dichloromethane dosis (X) of 1--6 mmole/kg administered i.p. to rats and the sciatic motor conduction velocity (Y): Y = 57.1--1.091 X. The correlation coefficient 'r' is 0.437 (p less than 0.01). Presumably, the decrease of nerve conduction velocity is caused by the endogenous carbon monoxide production due to dichloromethane biotransformation.


Cell death and phagocytosis in the neuroepithelium of the developing retina. A TEM and SEM study.

Phagocytosis by neuroepithelial cells independent of the presence of pseudopodes is observed as the main mechanism of elimination of physiologically degenerating cells during the early development of the retina in the chick embryo.


Cholinesterase in the atherosclerotic intima and in fibroblast cultures.

Cholinesterase activity was present in the atheromatous plaque of the rabbit's atherosclerotic aorta. Cholinesterase activity was significantly increased in rat fibroblast cultures grown in the presence of hypercholesterolemic serum. Cholesterol ester synthesis in these cultures was inhibited by neostigmine, a cholinesterase inhibitor.


Induction of lymphomas by urethane in combination with diethylstilboestrol in CFLP mice.

The combination of urethane and the non-steroidal oestrogen diethylstilboestrol induced lymphomas in CFLP mice.


Quantitative histological study of spinal afferent innervation on the ventral surface of the cat stomach by horseradish peroxidase (HRP) method.

Retrograde axonal transport of horseradish peroxidase (HRP) was applied to the ventral surface of the cat stomach. We investigated the number, size and distribution of HRP-positive cells in spinal ganglia. The unexpected finding was the wide distribution of these cells from T3 down to L3. This would result in a diffuse pattern of referred pain.


Demonstration of cross reaction between anti-macrophage antibodies and mononuclear mesodermal cells.

An anti-macrophage antiserum to rat peritoneal macrophages was prepared in rabbits. The antibodies produced showed cross reaction with perivascular adventitial macrophages, with macrophages in thymus and spleen, and with brain microglial cells.


Carcinogenicity examination of betel nuts and piper betel leaves.

A dry powder of betel nuts, piper betel leaves and lime was administered to rats. Epidermal thickening was frequently observed in the upper digestive tracts of rats in groups fed the betel nut diet mixed with lime and the betel leaves diet, and a forestomach papilloma was seen in 1 rat given betel leaves diet. These epidermal changes were scarcely seen in rats given either betel nut or normal diet alone.


Effects of 9.4 GHz microwave exposure on meiosis in mice.

Exposure to 9.4 GHz pulsed microwaves at low power densities for 1 h/day during 2 weeks induces in adult male Balb/c mice disturbances in meiosis, consisting in an increase of translocations and the appearance of cells with several chromosome pair remaining univalents at MI.


Quantitative ultrastructural features of maturing mononuclear phagocytes in rat peritoneal fluids.

Ultrastructural features of the in vivo transformation of macrophage congeners in resident and adjuvant-induced peritoneal populations are evaluated by sterological methods. Maturation involves an increase in cell size by the differential hypertrophy of subcellular compartments, notably remaining cytoplasm, nucleus and lysosome-like granules. Larger cells have more and larger granules, more mitochondria and a greater plasmalemmal surface. In contrast, adjuvant activation tends to produce fewer granules and a nett loss of surface membrane.


Frequency and distribution of tubulo-filamentous nuclear inclusions in the celiac ganglion of the cat as revealed by serial sections.

On sections at random of a cat celiac ganglion we counted 68 sections of nuclear inclusions (NI) for 320 sections of neuronal nuclei, i.e. an "apparent' frequency of 0.20. As revealed by serial sections the "actual' frequency is higher since the 5 nuclei entirely explored exhibit 19 NI. Such a study shows that each nucleus may contain at least 3 and up to 5 different tubulo-filamentous NI.


Prefrontal cortex of the cat: evidence for an additional area.

Direct projections from the mediodorsal nucleus of the thalamus to ventral parts of the insular region of the cat's cortex were demonstrated by using the horseradish peroxidase technique.


Changes in the plasma membrane surface of lymphocytes stimulated in vivo with DNCB.

Stereological principles have been used to evaluate ultrastructural changes which accompany the transformation of lymphocytes stimulated in vivo with dinitrochlorobenzene (DNCB). Whereas unstimulated lymphocytes and blast cells have slightly more than the minimal containing plasmalemmal surface for their volume, stimulated (blast-derived) lymphocytes have an excess surface area in the order of 30%. This observation is discussed in the context of altered cell function and the biosynthesis of additional membrane components.


Innervation of the ovarian interstitial cell of the chick embryo.

Electron microscopic examination of the developing ovary of 15-20-day chick embryos revealed that the interstital cells well innervated. Nerve fibres and nerve endings were observed in close contact with steroid-producing cells.


Effect of colicin E3 on leukemia cells P388 in vitro.

Proliferation of murine leukemia cells P388 is stimulated by less than 1.0 mg/ml colicin E3, while being inhibited by higher concentrations. By 1.6 mg/ml colicin E3, uptake of thymidine into cold TCA-precipitable fraction is decreased by 59% during 24 h, uptake of uridine by 29%.


Reduction of serum X-prolyl dipeptidyl-aminopeptidase activity in tumour-bearing mice and reversal of reduced enzyme activity by lentinan, an anti-tumour polysaccharide.

Serum X-prolyl dipeptidyl-aminopeptidase activity which had been shown to be depressed in cancer patients was clearly reduced in mice with Ehrlich carcinoma and Sarcoma 180, and slightly reduced in mice with methylcholanthrene-induced sarcomas. The reduced enzyme activity was completely reversed during tumour regression of sarcoma 180 by administration of lentinan, which causes regression of sarcoma 180.


Local adjuvants: the influence of sodium dodecylbenzene sulphonate on immunization with aerosolized antigen.

Guinea-pig respiratory and serum antibody responses were enhanced following exposure to aerosols of bovine IgG2 dissolved in solutions of sodium dodecylbenzene sulphate (SDBS). Enhanced response was seen in both primary and secondary immunization. Cell-mediated immune response (indirect macrophage migration influencing test) was not altered by SDBS. Results are discussed with a view to the possible utility of SDBS as adjuvant for prophylactic immunization.


Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America.

Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.


A study of the enzyme activity in the seminal vesicles of castrated and hormone-replaced castrated mice.

Castration provokes a time-related decrease in weight, protein, beta-glucuronidase and glucose-6-phosphate dehydrogenase activity of seminal vesicles. A dose-dependent stimulation of these parameters is obtained with 5alpha-DHT. Cryproterone acetate counteracts the stimulatory effects due to androgen. Acid and alkaline phosphatases remain largely unaffected by these treatments.


A new simple assay for total blood lipids by refractometry.

A fast simple method for assay of total blood lipids has been devised by precipitating blood proteins with methanol and extracting lipids into diethyl ether. The change in refractive index of the methanol-ether due to dissolved lipids is measured in a refractometer.


The morphology of cytoplasts and karyoplasts produced by cytochalasin D.

The denucleation of L cells and human lymphocytes in suspension was carried out by incubation with cytochalasin D25 and 50 microgram/ml and with ultracentrifugation over a discontinuous Ficoll gradient. Ultrastructural examination of the separate layers confirmed the presence of the anucleate cytoplasm (cytoplasts) with intact membrane and the separated nuclei (karyoplasts).


Sectioning of polyacrylamide slab gels with a modified small animal stereotaxic instrument.

A simple and inexpensive modification of the Kopf model 900 small animal stereotaxic instrument allows it to be used temporarily as a precision polyacrylamide slab gel slicer.


Leonurine, an improved synthesis.

Leonurine (1) is the uterotonic principle of Leonurus artemisia. We have developed a simple, high-yield synthetic procedure of 1 that is adaptable to large scale preparation. The synthesis involves the condensation of syringic acid and 4-guanidino-1-butanol hydrochloride in the presence of DDC using 1:1 HMPT-ether as solvent. The synthetic leonurine showed uterotonic activity in vivo and in vitro.


Altered or increased transfer-RNA methylation in the course of Interferon action on cells in culture?

The induction of the antiviral state by Interferon might reflect the decrease of the rate of biosynthesis, the degradation or the alteration of one or several tRNAs. This could result in rate-limiting concentrations for codons common in viral RNA but rare in host mRNA. Altered methylation of tRNA could be the basis of such a phenomenon. However, we could not find an altered extent of methylation of total tRNA or an altered pattern of methylation, if mixed tRNAs were chromatographed on MAK- or BD-cellulose columns, despite a large range of conditions of pretreatment of chick embryo fibroblast cultures with interferon.


Polyamines as activators of AMP nucleosidase from Azotobacter vinelandii.

Polyamines at physiological concentrations activate AMP nucleosidase from Azotobacter vinelandii. Biological significance of the activation is discussed in relation to the control of adenylate energy charge and the purine nucleotide synthesis in prokaryotes.


Circadian activity of rat kidney enzymes.

Alkaline phosphatase, LAP, beta-glucuronidase and cathepsin D activities and protein content of the kidney homogenate did not show any circadian rhythm in animals sacrificed at different hours of the day. The fluctuations of maltase appear modest and not dependent on a ligh/dark cycle.


Diethylmesoxalate hydrate, a new irreversible inhibitor of cholinesterases.

Bovine erythrocyte acetylcholinesterase and human plasma cholinesterase are irreversibly inhibited by diethylmesoxalate hydrate, the inhibition potency being comparable to that of certian insecticidal organophosphates and carbamates. Insect cholinesterases, however, appear to be much less affected by diethylmesoxalate hydrate. The compound was also found to inhibit the hydrolysis of paraoxon by rabbit plasma A-esterase, but in a reversible mode.


Effect of solubilization of Salmonella minnesota Re glycolipid on its interferon-induced activity.

Electrodialysis of Salmonella minnesota Re glycolipid, or exposure to 0.2 M EDTA, pH 7.0, yields products capable of eliciting interferon production at concentrations 10-fold lower than that of the original glycolipid.


Persistence of body weight cycles in dormice maintained with a limited food supply.

Dormice kept under food restriction for several months continued to exhibit body weight cycles with characteristic periods of about 2 months, despite an impaired ability to attain the high body weight levels observed in ad libitum conditions. These results imply that the cycle is controlled by a mechanism whose properties are more consistent with asn endogenous oscillator than with a sequence of stages, in which the relevant stages are defined by upper and lower body weight limits.