[Bronchial asthma due to occupation allergy of immediate type (I) to platinum salts (author's transl)]. Occupational inhalation allergy (bronchial asthma, rhinitis, conjunctivitis), often in association with urticaria and Quincke oedema is common in platinum associated industry. It is due to sensitization against platinum chloride. The reaction mechanism corresponds to the immediate type (I) allergy as shown by clinical tests (skin tests), in virtro (histamine release from leucocytes) and in vivo investigations (passive cutaneous anaphylaxis in apes). The degree of sensitization is so high that test investigations in affected persons must be performed with care. For prick testing with platinum chloride (PtCl6)2- or (PtCl4)2- an initial concentration of 10(-9) g/ml is recommended. As an average of 60% of people working in the platinum industry fall ill with bronchial asthma more stringent protective occupational measures are suggested.


[Planning the teaching of pediatrics in the community]. Medical education today includes planning as a useful tool for guiding, and thereby improving, the teaching-learning process. Community work has become increasingly important in medical education programs, and planning is essential to it. One excellent field for these activities is pediatrics. This article analyzes the concepts of medical, health, and health care instruction in the community, and traces the emergence of this approach as a response to sociopolitical phenomena. The pediatric field is defined in terms of growth and development, disease hazards and the prevalent pathology, and the cultural and socioeconomic factors involved. Also considered are objectives, planning areas, and operational decentralization, and the methodology of community instruction on the level of the individual, the family, and the educational institutions, with varying degrees of community participation.


[Survey of medical practice: therapeutic applications and iatrogenic implications]. This survey sought to investigate and quantify the use of analgesics and the understanding of their therapeutic hazards. One hundred physicians from different fields and specialties practicing in São Paulo were queried as to the frequency of their use of these products and about their knowledge of the contraindications and the precautions to be taken, measured in percentages on the basis of information supplied by the producing laboratories themselves. The data were processed electronically, and the results bore out the immediate necessity of disseminating greater information on the side effects of these drugs among physicians, health authorities, and the general public.


Preliminary investigation of bilharzial patients for the presence of Australia antigen using latex agglutination test. THE AUSTRALIA antigen was studied by the use of a reversed passive latex agglutination test in the sera of 250 cases, mostly bilharzial. The results were analysed in relation to age, clinical presentation, bilharzial infestation, antibilharzial treatment, jaundice and serum bilirubin. It was found that, the test was significantly more positive in hepatosplenic cases, in those with past history of bilharziasis, in those with jaundice and in those with higher serum bilirubin level. While no significant difference was found in relation to age, and to history of antibilharzial treatment.


Behaviour of hepatitis B antigen in bilharzial patients infected with HBs positive viral hepatitis. A TOTAL of 204 cases with acute viral hepatitis were studied: 93 bilharzial and 111 non-bilharzial. This study is concerned with the 106 cases showing positive HBS Ag test. Follow up of the cases after discharge from the Fever Hospital was carried out by repeated clinical and laboratory examinations 3 montly in the first year and 6 monthly subsequently. The bilharzial and non-bilharzial patients were found to be equally susceptible to HBS Ag positive hepatitis (p=0.25). However, antigenaemia tended to last longer as a whole in the bilharzial patients (p=0. 005) and was not affected by successful specific antibilharzial treatment. It seems that bilharzial infection predisposes to "retention" of HBs antigen, after subsidance of the acute attack, thus increasing the volume of reservoir for HB virus in our rural community.


Effect of niridazole on the lipid pattern of the parasite and host tissues in experimental schistosomiasis mansoni. THE LIPID pattern of blood and liver of mice infected with S. mansoni as well as in male and female worms was studied. Experiments were also carried out on non-infected and infected mice after treatment with Niridazole. It was found that Niridazole caused a significant increase in liver triglycerides and serum free acids. These changes were more pronounced in non-infected animals than in infected ones. The drug was found to reduce worm phospholipids and to increase their triglyceride level. The male worms were more affected than the female ones.


Assumption of linearity in dose--effect relationships. As a basis for establishing radiation protection standards, a substantial amount of quantitative information is now available on the frequency with which malignant diseases are induced in man by moderately high doses of radiation. Such estimates can now be made not only for irradiation of the whole body but also for exposure of a number of body organs individually. The frequency with which cancers might follow the much lower doses involved in occupational or environmental exposure to radiation, however, cannot be derived from any available epidemiological surveys. It can at present only be inferred by the (probably pessimistic) assumption that the frequency of such effects is linearly proportional to the size of dose received, even down to the lowest doses. Increasing information as to the probable form of the actual dose--effect relationship for radiation is indicating the extent to which the use of this "linear hypothesis" may overestimate the risk of low doses as inferred from the observed risk of higher doses. A linear hypothesis has been used in the same way for estimating the likely frequency of harm from low doses of chemical substances which have defined harmful effects at high dose. The appropriateness of this procedure depends critically upon the way in which chemical pollutants, or the relevant products of their metabolism in the body, are likely to become distributed through body tissues and cause the relevant harmful effects on cells.


Experimental identification of chemical carcinogens, risk evaluation, and animal-to-animal correlations. Experimental methods for the identification of chemical carcinogens have been extensively developed, including animal bioassay methods, animal models for cancer induction at major organ sites, models for the study of the effects of carcinogens in cells and tissues in culture and methods for the study of molecular events (metabolic activation, binding and detoxification of carcinogens; DNA damage and repair; mutagenicity). Current sources of documentation on carcinogenicity data are reviewed. The number of "known carcinogens" will vary considerably, depending on the criteria adopted for accepting evidence of carcinogenicity. CRITERIA FOR THE EVALUATION OF RISKS, BENEFITS, AND TECHNOLOGICAL ALTERNATIVES FOR PUBLIC POLICY ON ENVIRONMENTAL CARCINOGENS ARE REVIEWED AND THE FOLLOWING STEPS DISCUSSED: registration of environmental chemical carcinogens and their uses; risk evaluation (considering sources, adequacy, quality and limits of the evidence; quantitative dose-response extrapolation within the same biological system; and species and model conversion factors); benefits evaluation; analysis of technological alternatives; comparative judgment and decision; open public documentation. The problem of animal-to-human correlations is considered, particularly for respiratory carcinogenesis. A laboratory approach is reviewed which includes: development and study of whole animal models for carcinogenesis, analysis of animal tissue responses to carcinogens in vivo and through in vitro culture methods for morphological and biochemical studies, and development of in vitro culture methods for human target tissues. This approach is aimed at providing an experimentally controlled and quantifiable method for the correlation of animal and human observations in carcinogenesis.


Estimating cancer risks to a population. Three important issues impinge on estimating the risk of cancer to a population: (1) How can one use epidemiologic studies on one population to tell us what is likely to happen to other populations? (2) How can one use nonhuman data (i.e., laboratory experiments) to tell us what is likely to happen to humans? (3) What reasonable assumptions can be used to guide the logical extension of information from the laboratory to expectations for man, and what research is needed to support or modify these assumptions? Four principles currently guide our laboratory-to-man extrapolations: effects in animals, properly qualified, are applicable to man; methods do not now exist to establish a threshold for long-delayed effects such as cancer; the exposure of experimental animals to high doses is a necessary and valid method of discovering possible carcinogenic hazards in man; materials should be assessed in terms of human risk rather than as "safe" or "unsafe".


Approaches for protection standards for ionizing radiation and combustion pollutants. The question "can the approach used for radiation protection standards, i.e., to extrapolate dose--response relationships to low doses, be applied to combustion pollutants?" provided a basis for discussion. The linear, nonthreshold model postulated by ICRP and UNSCEAR for late effects of ionizing radiation is described and discussed. The utility and problems of applying this model to the effects of air pollutants constitute the focus of this paper. The conclusion is that, in the absence of evidence to the contrary, one should assume the same type of dose--effect relation for chemical air pollutants as for ionizing radiation.


The "urban factor" and lung cancer: cigarette smoking or air pollution? Data are presented which suggest that cigarette smoking, and to a lesser degree, urban pollution as indexed by benzo[a]pyrene are etiologic factors in the causation of lung cancer. The dose--response relationship to benzo[a]pyrene to lung cancer death rate in the urban community was estimated by using data on lung cancer deaths among coke oven workers. It appears to be an excess of 2--5 mumg/m3 of benzo[a]pyrene per 100,000 population, suggesting that a lifetime community exposure to benzo[a]pyrene on a continuing basis may have a greater impact on lung deaths in the community than that considered by the Royal College of Physicians.


Atmospheric pollution and lung cancer.

Atmospheric pollution and lung cancer. Lung cancer is consistently more common in urban areas than in rural. The excess cannot be accounted for by specific occupational hazards but some of it might be due to the presence of carcinogens in urban air. The excess cannot be wholly due to such agents, because the excess in nonsmokers is small and variable. Cigarette consumption has also been greater in urban areas, but it is difficult to estimate how much of the excess it can account for. Occupational studies confirm that pollutants present in town air are capable of causing lung cancer in man and suggest that the pollutants and cigarette smoke act synergistically. The trends in the mortality from lung cancer in young and middle-aged men in England and Wales provide uncertain evidence but support the belief that atmospheric pollution has contributed to the production of the disease. In the absence of cigarette smoking, the combined effect of all atmospheric carcinogens is not responsible for more than about 5 cases of lung cancer per 100,000 persons per year in European populations.


Extrapolation of carcinogenic risk from animal experiments in man. When estimating the absolute risk of cancer, the shape of the dose--response curve in the region of doses where actual exposure of man occurs is of crucial importance. This shape is equally important for the determination of relative risks, as in the comparison of risks from alternative energy sources. Experimental and epidemiological studies are, for various reasons, unable to give sufficiently exact information concerning the dose response in the low dose region. Therefore, the discussion concerning dose--response relationships also has to consider biologically reasonable mechanisms for the origin of tumors.


General subcellular effects of lead, mercury, cadmium, and arsenic. This working paper summarizes the known ultrastructural and biochemical effects of lead, mercury, cadmium, and arsenic on subcellular organelle systems following in vivo administration. Documented metal-induced alterations in nuclear, mitochondrial, microsomal, and lysosomal functions are discussed in relation to their potential impact on cellular responses to other environmental agents. Each of the above elements has been found to interfere with normal cellular replication and genetic processes. Mitochondrial swelling and depression of respiratory function are discussed in relation to known metal-specific perturbations of mitochondrial heme biosynthetic pathway enzymes. Inhibition of microsomal enzyme activities and protein synthesis by lead and mercury is compared to the apparent absence of such effects following arsenic or cadmium exposure. Lysosomal uptake of all the metals is documented, but biochemical alterations in these structures have been reported for only mercury and cadmium. It is concluded that these toxic metals are capable of interacting with, and biochemically altering major cellular systems at dose levels below those required to produce signs of overt metal toxicity. The impact of these effects on cellular response to other metals and xenobiotics in complex exposure situations is presently unknown, and further research is urgently needed in this area.


Relevance of short-term carcinogenicity tests to the study of the carcinogenic potential of urban air. It is now accepted that screening for carcinogens in animals is expensive and demonstrates carcinogenic potential rather than actual carcinogenicity in man. A number of short-term tests which depend on mutagenicity, stimulation of DNA repair, ability to produce chromosome damage or other actions, and which correlate at least to some extent with carcinogenic potential, have been devised. These have the advantages of being rapid and cheap. Some can be carried out by using human cells. They may have advantages in the context of air pollution since they are sensitive down to very low dose levels and since they can deal with complex mixtures. Combinations of such tests may be of more value than any single test. Their particular value may be as a preliminary screening procedure in a tiered testing programme which may have high predictive efficiency.


Trends in urban air pollution in the United Kingdom in relation to lung cancer mortality. The substantial reduction in air pollution, and particularly in components such as benzo[a]pyrene in urban areas of the United Kingdom during the past few decades has presented an opportunity to consider further the possible role of carcinogens in the air in relation to lung cancer. While the overall trends in lung cancer mortality have undoubtedly been dominated by changes in smoking, the marked contrasts that at one time existed between these death rates in urban and rural areas have gradually diminished. This may indicate that air pollution contributed appreciably to the urban/rural differences in lung cancer at one time, but it is still difficult to disentangle any effects it may have had from those of changing smoking habits.


Dose assessment analogies.

Dose assessment analogies. Assessments of radiation detriment are based on the absorbed dose in the organs and tissues of interest, assuming a linear, nonthreshold dose--response relationship for the induction of cancer or genetic effects at low doses. Similar assessments may be made for nonradioactive, mutagenic, or carcinogenic substances, in which case the time integral of the local tissue concentration of the substance may be the quantity which would correspond to the radiation dose. It can be shown that the assessment then involves calculations which are very similar to those made in the assessment of radiation detriment. It is suggested that an attempt should be made to make such assessments for nonradioactive pollutants, in order to provide a more appropriate basis for comparisons with radiation detriments. In the assessment of the detriment from inhaled substances, the overall collective intake commitment is simply the total amount of each substance ever to be inhaled, irrespective of when or where. This quantity might be assumed to be proportional to the total detriment in form of lung cancer.


Potentially carcinogenic species emitted to the atmosphere by fossil-fueled power plants. The identities and physicochemical characteristics of potentially carcinogenic species emitted to the atmosphere by fossil-fueled power plants are presented and discussed. It is pointed out that many so-called carcinogens are preferentially concentrated on the surface of respirable fly ash particles thus enabling them to come into intimate contact with lung tissues when inhaled. Relatively little information is available about the identities of particulate polycyclic organic compounds whose emission from coal fired power plants may well be substantially greater than hitherto supposed. The importance of chemical changes, which several species may undergo following emission (but prior to inhalation) in determining their potential carcinogenic impact, is stressed.


Possible mutagenic properties and carcinogenic action of the irritant gaseous pollutants NO2, O3, and SO2. Carcinogenic or cocarcinogenic effects of NO2, O3, and SO2 have not been proven to date with sufficient reliability. However, nitrosamine formation after exposure to NO2- or O3-induced decrease in benzpyrene hydroxylase are potential hazards. A final revaluation of a possible cocarcinogenic action of SO2 requires further experimental studies.


Comments on extrapolation of cancer response from high dose to low dose. In making judgments as to the cancer risk from low level exposure to carcinogens it is generally necessary to base these judgments on high dose or high incidence data from laboratory or epidemiological studies. The biological considerations involved in making such extrapolations are discussed, as well as some of the mathematical procedures. The difficulties presented by moving from species to species, or from differently acting carcinogenic agents is considered.


Fundamental aspects of dose--response relationships and their extrapolation for noncarcinogenic effects of metals. Fundamental differences in dose--response relationships between "stochastic" and "nonstochastic" effects of chemicals are identified and discussed. The difficulties in extrapolating into the low-dose region of dose--response curves are pointed out. In some instances of nonstochastic effects, observations concerning interindividual variability in biological half-time and threshold body burden for symptoms may be used for such extrapolation. An example based on data from the literature concerning effects of methyl-mercury on the nervous system is given. The confidence intervals of the extrapolated risk-values are computed and discussed in relation to assumptions concerning the mathematical model to be used in the extrapolation process.


Treatment of traumatic arthritis in the horse with intra-articular orgotein (palosein). A total of 134 horses of various breeds were treated for aseptic arthritis of traumatic origin using Orgotein (Palosein). The drug was injected into 192 affected joints of these animals. Recovery rates of 94 per cent were recorded in cases which had shown lameness for less than 2 months before treatment commenced and 49 per cent in those lame for longer than 2 months.


A study of the hearing ability of horses. The ability of 10 horses to hear frequencies between 14 and 25 Kc/s was tested. The horses appeared to perceive ultrasounds by showing either fright reactions or Pryer reflexes to all of the 12 frequencies. The highest frequencies were heard less by older animals, and elicited more reactions in geldings than in mares.


Influence of heavy weight carrying on the cardiorespiratory system during exercise. To study the influence of weight carrying on the cardiorespiratory system during dynamic exercise (walking) four conditions, i.e., rest, and treadmill exercise at 25, 50, and 75% of the individual VO2max, were combined with weight carrying of 10, 20, and 30 kg. In all experiments oxygen uptake, heart rate and pulmonary ventilation were measured. For each dynamic exercise condition and for the rest condition regression lines are calculated showing the relation between weight load an oxygen uptake, heart rate and pulmonary ventilation. From the slopes of these regression lines it can be seen that in rest (standing position) weight carrying does not influence oxygen uptake, heart rate and pulmonary ventilation. In dynamic exercise oxygen uptake, heart rate and pulmonary ventilation increase linearly with the amount of weight carried. To a large extent this increase is independent of the dynamic work load. In this study it was found that each kilogram extra weight increases oxygen uptake with 33.5 ml/min, heart rate with 1.1 beats/min and pulmonary ventilation with 0.6 1/min. In dyanmic work for loads higher than 50% of VO2max the relationship between weight carried and pulmonary ventilation is no longer a linear one. For the subjects studied it is assumed that oxygen consumption per kilogram weight is not different for body weight or extra weight carried.


Energy metabolism in different human skeletal muscles during voluntary isometric contractions. The energy turnover in contracting skeletal muscle was studied by measuring the rate of temperature rise during voluntary, isometric contractions and circulatory arrest in M. soleus, M. sacrospinalis and M. biceps brachii in 14 males, by thermoelements inserted in the muscles. A linear relationship between rate of temperature rise and force intensity given as per cent of maximal voluntary contraction (MVC) was demonstrated in biceps (r = 0.95), but not so clearly confirmed in soleus  (r = 0.73). Muscle biopsies were taken from the same muscles and fibre type distribution was determined histochemically by staining for ATPase. The rate of heat production at MVC showed positive correlation to the percentage of fast twitch (FT) fibres in the muscles (r = 0.90). Linear extrapolation indicates that the maximal energy turnover in human FT fibres is approximately six times that of slow twitch (ST) fibres during voluntary isometric contractions.


Segmental contribution to forces in vertical jump. Performance of a vertical jump was analyzed with respect to the contribution of the different body segments to the forces acting on the whole body center of gravity. Both cinematograph and force-platform techniques were employed. The data disclosed that the take-off velocity in vertical jumps was caused by the different components as follows: knee extension 56%, plantar flexion 22%, trunk extension 10%, arm swing 10%, and head swing 2%. However, the average take-off velocity of the total performance (3.03 m/s) was only 76% from the theoretical maximum calculated from the segmental analyses. Optimal timing of the segmental performances was calculated to increase this "efficiency" to 84%. Great variance were observed among individuals in the total performance despite the similarities in utilization of the performance of individual segments.


Muscle strengths in relation to fat storage rate in young men. Hand-grip strength, elbow flexion strength, trunk extension strength and knee extension strength, and body composition (measured by densitometry) were measured in 59 male students (mean 19.2 years) in order to compare the muscle strength of obese men, in relation to fat storage rate (% fat), with those of non-obese men. Their % fat ranged from 6.2-35.6%. Correlations of body weight and lean body mass were found to be significant with each muscle strength. Our findings presented that obese men had lower muscle strengths for body weight and lean body mass than non-obese men do. This might be the result of two characteristics, inactivity and weak willpower, of obese men. Besides, the 20% fat of threshold of obesity for men proposed by Behnke and Wilmore was reasonable from the viewpoint of the muscle strength because of the differences between group D (18.8% fat) and group E (23.8% fat).


Splenic storage volume in the unanesthetized resting beagle. Determination of the dog's splenic storage volume without surgical procedures requires measurement of both circulating and total red cell volumes. The estimation of circulating red cell volume by radioisotope techniques is impeded by the rapid uptake of tagged cells in the spleen. The circulating cell volume might be calculated from plasma volume and large vessel hematocrit, provided that the latter is corrected for the unequal distribution of red cells in the circulatory system. However, the correction factor can only be estimated in the splenectomized dog. We describe here a method to determine the factor in the intact dog, "physiologically splenectomized" by the severe exercise. The values obtained by this method slightly exceed those in the resting dog, as shown by studies in splenectomized exercising beagles in which splenic function was simulated by infusion of packed cells. The method was tested in beagles exercised by swimming and treadmill running and it was concluded that in the unanesthetized resting beagle about one-third of all erythrocytes is stored in the spleen. Labeled cells are equilibrated with about one-half of the splenic storage volume within 10 min after their injection. During maximal exertion the mean increase in large vessel hematocrit was 38.6 +/- 3.3%, the mean decrease in plasma volume 13.6 +/- 1.7% and the mean increase in plasma osmolarity 2.8 +/- 0.9% (percentages of control values).


Studies on vasodilatation in the hand on exposure to heat. In five subjects whose hands were exposed to heat, no depletion in the plasma kininogen level was observed when vasodilatation occurred. This might be due to the admixture of arterial and venous blood following the opening of arterio-venous (A--V) anastomoses. The small rise obtained by warming was not significant (P greater than 0.1). Consequently, the drop in kinonogen concentration recorded when the hand was allowed to cool to an ambient temperature of 23 degrees C as compared with the basal level and that during the period of warming, was also found to be non-significant. In another nine subjects whose A--V kininogen values were determined when their hands were immersed in a water bath at 37 degrees C, a significant A--V difference of the kininogen content was obtained. From this work, it is concluded that no appreciable depletion of venous kininogen concentration was obtained on hand warming. It is possible that sweat glands, vasodilator nerve fibres and the release of kinins contribute in part to the dilatation that occurs. Possible patho-physiological mechanisms involved are discussed.


Predicting metabolic cost of level walking. Energy expenditure in walking is usually expressed as a function of walking speed. However, this relationship applies only to freely adopted step length-step rate patterns. Both the step length and the step rate must be used to preduct the energy expenditure for any combination of step length and step rate. Evidence on seven subjects indicates that the energy demand for such a combination can be determined by conducting two experiments. In the first, the subject is allowed to freely choose his own walking pattern to achieve a set of prescribed speeds. In the second, the speed is kept constant but the subject is forced to adopt a range of prescribed step rates. The results of the two experiments combined yield enough data to make possible the determination of the energy equation of the pattern, encompassing both "free" and "forced" gaits. Results show that the freely chosen step rate requires the least oxygen consumption at any given speed. Any other forced step rate at the same speed increases the oxygen cost over that required for the "free" step rate.


Conformation of methylated sequences in HeLa cell 18-S ribosomal RNA: nuclease S1 as a probe. 18-S rRNA from HeLa cells was digested with nuclease S1. Under the conditions employed 15% of the total nucleotides and some 50% of the methylated nucleotides were released as low-molecular-weight products. The material which was precipitable by 70% ethanol after nuclease S1 digestion was subjected to further digestion by combined T1 plus pancreatic ribonucleases or by T1 ribonuclease alone, and fingerprints were prepared. It was found that the four sites which are modified late during ribosome maturation, and which contain base modifications, were all accessible to nuclease S1. By contrast fewer than one-half of the sites which are modified early during ribosome maturation, and which contain 2'-O-methyl groups, were accessible to nuclease S1; the remainder were protected, presumably by secondary or tertiary interactions within 18-S rRNA.


Glyceroglucolipids of the human saliva.

Glyceroglucolipids of the human saliva. Seven individual glycolipids (I--VII) have been isolated from the lipid extract of human saliva. All glycolipids contained glucose, glyceryl ethers and fatty acids, and differed from each other primarily with respect to the number of glucose residues. In addition, glycolipid V contained also the sulfate ester group. The structures of these glycolipids were identified by partial acid and alkaline hydrolysis, oxidation with periodate and chromium trioxide and methylation studies, as: Glc(alpha1 leads to 3)-diglyceride (glycolipid I), Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipids II and III), Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid IV), SO3H-6Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid V), Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid VI) and Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 6)Glc(alpha1 lead to 6)Glc(alpha1 leads to 6)Glc(alpha1 leads to 3)-diglyceride (glycolipid VII). Diglyceride portion of these compounds consists of 1-O-alkyl-2-O-acyl-glycerol with the docosanoate and glyceryl-monodocosyl being the predominant acyl and alkyl components.


Inhibition of yeast phosphatidic-acid synthesis by free fatty acids. Particulate preparations obtained from cells of yeast Saccharomyces sake have been shown to possess glycerolphosphate acyltransferase and 1-acylglycerolphosphate acyltransferase activities. Glycerolphosphate acyltransferase exhibits a high specificity for saturated and monoenoic fatty acyl-CoA thioesters. When palmitoyl-CoA is employed as sole acyl group donor, the major lipid product is lysophosphatidic acid. 1-Acylglycerolphosphate acyltransferase of this yeast species has a rather strict specificity for monoenoic fatty acyl-CoA thioesters as acyl donor. These two acyltransferases are strongly inhibited in vitro by low concentrations of free fatty acids. 1-Acylglycerolphosphate acyltransferase is much more susceptible to fatty acid inhibition than glycerolphosphate acyltransferase. The inhibition is dependent not only on the concentration of fatty acid, but also on the length of exposure to fatty acid. Both saturated and unsaturated fatty acids inhibit the acyltransferase activities. The inhibitory effects of fatty acids cannot be ascribed to a nonspecific surfactant action of fatty acids. The present results support the view that free fatty acid serves as a regulator of glycerolipid synthesis.


Photochemical modifications of the tryptophan residues of wheat-germ agglutinin in the presence of trichloroethanol. Trichloroethanol is an efficient quencher of indole fluorescence of model compounds and proteins [Eftink, M. R. and Ghiron, C. A. (1976) J. Phys. Chem. 80, 486--493]. At low quencher concentrations, the quenching follows the classical Stern-Volmer law. Bimolecular rate constants calculated from measured quenching constants and lifetimes are equal to 6 X 10(9) M-1s-1 and 1.2 X 10(9) M-1s-1 for N-acetyltrypotophanamide and wheat germ agglutinin, respectively. Upon ultraviolet irradiation in the presence of trichloroethanol, transformation of fluorescent tryptophan occurs, leading to a fluorescent photoproduct. This can be easily used as a method for the quantitative determination of fluorescent tryptophan residues in proteins. In good agreement with previous results, two fluorescent tryptophan residues per polypeptide chain are found in wheat germ agglutinin. Concomitantly with the photochemical reactions, the hemagglutinating protein activity and its affinity constant towards chitin oligomers are reduced. A probable location of tryptophan residues in the binding sites of wheat germ agglutinin is proposed.


Reactions of antibodies against ferredoxin, ferredoxin-NADP+ reductase and plastocyanin with spinach chloroplasts. Purified antisera against ferredoxin, ferredoxin-NADP+ reductase and plastocyanin agglutinated osmotically shocked and washed spinach chloroplasts, prepared according to standard procedures. The monomeric antibody (immunoglobulin G fraction) of the reductase antiserum agglutinated chloroplasts specifically and directly, indicating that protruding structures (for example, the coupling factor) do not act as steric hindrances as has been suggested. With ferredoxin antiserum, the presence of a pentameric antibody (immunoglobulin M fraction) was obligatory to observe a positive agglutination reaction. Immunoglobulin G only inhibited ferredoxin-dependent reactions, like NADP+-photoreduction, but did not cause agglutination. Ferredoxin seems to be located in depressions of the membrane, possibly caused by a partial release of this protein in shocked chloroplasts. Similar results were obtained with purified immunoglobulins from a plastocyanin antiserum. Again the immunoglobulin G fraction inhibited electron transport reactions catalyzed by plastocyanin, whereas immunoglobulin M showed a positive agglutination, but had no influence on electron transport. It is concluded that ferredoxin, ferredoxin-NADP+ reductase and plastocyanin are peripheral electron transport components, located at the outer thylakoid membrane.


Active-site catalytic efficiency of acetylcholinesterase molecular forms in Electrophorus, torpedo, rat and chicken. The active sites of acetylcholinesterase multiple forms from four widely different zoological species (Electrophorus, Torpedo, rat and chicken) were titrated using a stable, irreversible phosphorylating inhibitor (O-ethyl-S2-diisopropylaminoethyl methyl-phosphonothionate). In all cases, we found that within a given species, the molecular forms we examined were equivalent in their catalytic activity per active site. As pure preparations of the molecular forms of Electrophorus acetylcholinesterase were available, we were able to establish that one inhibitor molecule binds per monomer unit for each of them. This had already been shown by several authors for the tetrameric globular form, but not for the tailed molecules. Analysis of the phosphorylation reaction showed that they are equally reactive. Under our experimental conditions, their turnover number per site was 4.4 x 10(7) mol of acetylthiocholine hydrolysed . h-1 at 28 degrees C, pH 7.0. The corresponding value was less than half for Torpedo (1.64 x 10(7) mol . h-1), and again lower for rat (1.32 x 10(7) mol . h-1) and chicken (1.05 x 10(7) mol . h-1). In the case of rat acetylcholinesterase, the activity per active site of solubilized (with or without Triton X-100) and membrane-bound enzyme were identical. We discuss the implications of these findings with respect to the quaternary structure of acetylcholinesterase, and to the physico-chemical state and physiological properties of its molecular forms.


Interaction of adenylosuccinate synthetase with F-actin. Both crude and purified preparations of adenylosuccinate synthetase from muscle were found to combine with, and dissociate from, muscle debris precipitated from a homogenate of the muscle with water. The binding and dissociation depended on ionic strength. Further study showed that the muscle enzyme was adsorbed to F-actin, but not to G-actin or myosin. The muscle-type enzyme from the liver also associated with F-actin, but the liver-type enzyme from the liver did not. In the absence of KCl the molar ratio of adenylosuccinate synthetase from skeletal muscle to actin monomer in F-actin in the complex formed was 1 to 4. From a Scatchard plot the dissociation constant was calculated to be 0.72 micrometer. The binding was maximal at pH 5.5-7 in 30 mM potassium phosphate buffer. The complex was completely dissociated in the presence of 0.21 M KCl. The physiological significance of this binding is discussed on the basis of these findings.


Affinity chromatography of phenylalanine hydroxylase. The structure of a pteridine adsorbent. 1. Four independent methods have established that the structure of a previously reported pteridine affinity adsorbent, 6,7-dimethyl-5,6,7,8-tetrahydropterin--CH-Sepharose, is 5(CH-Sepharosyl)-6,7-dimethyl-5,6,7,8-tetrahydropterin. 2. A novel reaction, the carbodiimide-promoted coupling of a carboxyl group to N-5 of a tetrahydropterin, is described. 3. Two novel adsorbents, 5-formyl-tetrahydrofolate--AH-Sepharose and 5-methyl-tetrahydrofolate--AH-Sepharose, are described which may be useful not only in the study of phenylalanine hydroxylase but also in the study of folate-metabolizing enzymes.


4-Aminobutyrate aminotransferase fluorescence studies. The kinetics of resolution of the pyridoxamine phosphate form of the enzyme 4-aminobutyrate aminotransferase were monitored by fluorescence spectroscopy. 2 mol pyridoxamine phosphate are released/mol enzyme, indicating that two molecules of cofactor are involved in catalysis. The apoprotein is reconstituted by addition of pyridoxal phosphate; the apparent rate constant corresponding to the formation of active species is not a linear function of the concentration of cofactor. A multistep mechanism is proposed for the reconstitution of 4-aminobutyrate aminotransferase. A slow phase of reactivation of the aminotransferase is observed when the apoprotein is allowed to reconstitute in the presence of pyridoxal kinase, ATP and pyridoxal. The enzyme 4-aminobutyrate aminotransferase is a dimeric protein made up of subunits of identical molecular weight. It is characterized by a rotational relaxation time of 110 ns. The dimeric structure does not dissociate into subunits over a wide range of protein concentration (4--0.2 micrometer) at neutral pH.


The carboxyl-terminal sequence of the heavy chain of a Hong Kong influenza haemagglutinin. The reduced carboxymethylated heavy chain (HA1) of a Hong Kong influenza haemagglutinin (H3) was digested with cyanogen bromide to give five peptides. The sequences of three of these peptides, together with the sequences of two methionine overlap peptides were combined to give the C-terminal 68-residue sequence of the heavy chain. Threonine is the C-terminal residue of the heavy chain, an unexpected result in view of the generation of the heavy and light chains by the proteolytic cleavage of a pro-haemagglutinin during virus assembly. Three half-cystine residues occur close together at positions 24, 48 and 52 residues in from the C-terminus. A carbohydrate group is attached to an asparagine residue 44 residues from the C-terminus; it contains 5 residues mannose and 2 residues glucosamine.


Nucleotide torsional flexibility in solution and the use of the lanthanides as nuclear-magnetic-resonance conformation probes. The case of adenosine 5'-monophosphate. In this article the single family of conformations of adenosine 5'-monophosphate (5'AMP) in aqueous solution previously obtained using the lanthanide ions as nuclear magnetic resonance (NMR) probes is shown to disagree with the conformational data available from independent NMR methods, such as coupling constant and nuclear Overhauser enhancement analysis. The original lanthanide experimental data is reinterpreted assuming the contribution of different conformers to the observed magnetic perturbations. The average conformation obtained for 5'AMP agrees quite satisfactorily with the other independent conformational information.


Conformational studies of some 2':3'-cyclic mononucleotides in solution by different nuclear-magnetic-resonance methods. The conformations of the 2':3'-cyclic mononucleotides of adenosine and cytidine in deuterium oxide has been studied at pH 2.3, using lanthanide ions as paramagnetic nuclear magnetic resonance (NMR) probes. It was not possible to find any single conformation for these molecules which accounts for the observed shift and relaxation data. This situation is in agreement with the interpretation of vicinal 1H-1H and 1H-31P coupling constants, which indicate that the ribofuranose and cyclic phosphate rings are in rapid equilibrium between different puckered forms. The interpretation of the lanthanide data in terms of an equilibrium between different conformations give average rotamer populations in good agreement with the coupling constant analysis. The conformations of these systems in aqueous solutions were found to be more flexible than in the solid state, where rigid planar ribofuranose rings have been observed. Adenosine 2':3'-monophosphate differs from cytidine 2':3'-monophosphate at the glycosidic link.


Isolation of phosphoglycerate kinases by affinity chromatography. A variety of Sepharose derivatives containing DL-O-phosphorylserine or adenosine nucleotides with different points of attachment, has been synthesized and tested for affinity to phosphoglycerate kinase. The most effective gels contained periodate-oxidized ATP or ADP bound via the ribose by hydrazone formation to adipoyl-dihydrazo-Sepharose. The effect of pH, magnesium and buffer ions on the binding capacity of the ATP derivative of Sepharose has been examined. Optimal elution of phosphoglycerate kinase was investigated using different combinations of adenosine nucleotides, 3-phosphogylcerate and magnesium ions. A method is presented giving conditions for the purification of phosphoglycerate kinase from different sources (spinach, human erythrocytes, human, rabbit and trout muscle). It includes extract preparation, affinity chromatography and gel filtration. The method is greatly superior to known isolation procedures by virtue of its technical simplicity, excellent yield (85-100%) and reproducability. The capacity of the ATP-ribosyl-adipoyl-dihydrazo-Sepharose was 5 mg phosphoglycerate kinase per 1 g of matrix. Polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate indicated that the final products are homogeneous. The phosphoglycerate kinases from different sources appear to have the same affinity for this ATP derivative of Sepharose, the same molecular weight and the same specific activity.


The redox potential of dithionite and SO-2 from equilibrium reactions with flavodoxins, methyl viologen and hydrogen plus hydrogenase. 1. It has been shown that redox equilibria can be formed between dithionite ion (plus SO-2) and (bi)sulphite, and the low-potential electron carriers flavodoxin and methyl viologen. The equilibria were established either by treating the oxidized electron carriers with dithionite, or by treating flavodoxin hydroquinone or methyl viologen semiquinone with (bi)sulphite. Similar redox equilibria were established between dithionite/(bi)sulphite and hydrogen using catalytic amounts of hydrogenase in the presence of a low-potential electron carrier. The effects of pH and temperature on the equilibria were determined. 2. The equilibria were analyzed to determine the redox potential of the dithionite/(bi)sulphite system. In accordance with the results of earlier kinetic studies, it was assumed that the reductant in dithionite solutions is the dissociation product SO-2. The calculated midpoint redox potential E' for the couple SO-2/HSO-3 at pH 7 and 25 degrees C was -0.66 V. The reductant is present largely as the dimer at concentrations of dithionite above about 10nM. Consequently, the midpoint potential, Em, of dithionite solutions becomes less negative as the concentration of dithionite is increased (deltaEm/deltalog S2O2-4 = 29 mV). The theoretical potential of a solution of 1 M S2O2-4 and 2 M (bi)sulphite at pH 7 was calculated to be -0.386V. This value is 59 mV more negative than that determined in 1911 by potentiometry, but considerably more positive than other values in the literature. The effects of pH on the equilibria showed that E' is controlled by the pK of (bi)sulphite at 6.9; the slope deltaE'/deltapH was -59 mV below the pK and -118 mV above the pK. The effects of temperature on the equilibria suggested that Em for dithionite changed by -1.6 mV/degrees C for a rise in temperature between 2 degrees C and 40 degrees C. If sodium dithionite is contaminated with small amounts of (bi)sulphite, its addition in large excess to a low potential electron carrier can cause oxidation of the carrier.


Isolation of the ADP/ATP translocator from beef heart mitochondria as the bongkrekate-protein complex. 1. The isolation of the ADP/ATP translocator from beef heart mitochondria as the bongkrekateprotein complex is described, using hydroxyapatite chromatography and gel filtration in Triton X-100 solution. 2. The inhibitor is bound to the protein prior to solubilization with detergent for protection against denaturation. Only the intact bongkrekate-protein passes easily through the hydroxyapatite column. Bongkrekate shileds the protein in contrast to carboxyatractylate only partially against proteinases present in the crude extract. 3. The isolated bongkrekate protein shows the same molecular weights in dodecylsulfate and Triton X-100, the same amino acid composition and the same isoelectric point as the earlier isolated carboxyatractylate-protein complex. It differs by its higher sensitivity against trypsin and thermolysin. 4. The identity of both proteins is demonstrated by interconversion of the bongkrekate-protein into the carboxyatractylate-protein. The process requires the catalysis by ADP or ATP, the natural substrates of the protein. 5. The formation of the extractable [3H]bongkrekate-protein complex in mitochondria requires the presence of ADP or ATP. 6. These data, the immunological studies presented earlier, and the differences in the reactivity of -SH groups of the isolated bongkrekate and carboxyatractylate complexes (to be published) indicate that both proteins represent different conformational states of the translocator protein (m-state and c-state).


The plastid membranes of barley (Hordeum vulgare). Light-induced appearance of mRNA coding for the apoprotein of the light-harvesting chlorophyll a/b protein. Illumination of dark-grown barley plants induces a massive insertion of the light-harvesting chlorophyll a/b protein into the developing thylakoid membrane. In addition to the onset of chlorophyll synthesis, light induces specifically the appearance of a prominent mRNA species which codes for a polypeptide of Mr 29500. This component was identified as a precursor of the apoprotein of the light-harvesting chlorophyll a/b protein. The precursor has an Mr larger than the authentic protein by approximately 4000. Studies of the chlorophyll-b-less mutant chlorina f2 of barley offer the first clue to the mechanism which controls the light-dependent mRNA formation. The induction of the mRNA coding for the aproprotein of the light-harvesting chlorophyll a/b protein does not seem to be linked directly to the assembly process of the light-harvesting structure and does not require chlorophyll b. It is proposed that light exerts its influence on the mRNA formation by a reaction which is different from the phototransformation of protochlorophyll(ide) to chlorophyll(ide).


Calcium metabolism and enzyme secretion in guinea pig pancreas. Uptake, storage and release of calcium in whole cells and mitochondrial and microsomal fractions. In isolated pancreatic acinar cells from the guinea pig stimulation of enzyme secretion by carbamoylcholine is slightly diminished in the absence of extracellular Ca. LaCl3 in a concentration, which does not influence the secretory response to carbamoylcholine, nearly completely abolishes 45Ca uptake by cells, indicating that Ca uptake is not necessary for secretion. In cells preloaded with 45CaCl2, addition of carbamoylcholine leads to an immediate release of 45Ca, which can be blocked by atropine or 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate and is not influences by LaCl3 in concentrations, which do not inhibit secretion. A similar release of 45CaCl2 from preloaded cells is obtained by addition of the mitochondrial inhibitors antimycin A, carbonylcyanide p trifluoromethoxyphenylhydrazone (FCCP), and oligomycin. Possibly due to markedly diminished ATP levels, neither antimycin A nor FCCP act as secretagogues, both compounds being inhibitors of secretion. Oligomycin, which decreases ATP levels only to 20%, stimulates secretion. Mitochondria and microsomes from pancreatic tissue are able to accumulate 45Ca. Mitochondrial 45Ca uptake can be driven by ATP or active respiration and is inhibited by NaN3, oligomycin, antimycin A or FCCP. Microsomal 45Ca uptake is ATP-dependent. NaN3 and mitochondrial inhibitors have no influence on microsomal 45Ca uptake, which is stimulated several-fold by oxalate. The results support the assumption, that in the guinea pig pancreas Ca mobilization from intracellular stores is necessary to initiate secretion. Due to their ability for an active accumulation of45Ca both mitochondria and microsomes could serve as intracellular calcium stores.


Myelin basic protein in cerebrospinal fluid from children. Forty-one cerebrospinal fluid (CSF) specimens from children were investigated with a radioimmunoassay for their content of myelin basic protein (BP). Eight specimens were regarded as BP-positive (BP is greater than or equal to 1.0 ng/ml). Twenty-nine were BP-negative and 4 could not be analyzed because of an excessive protein content. The BP-positive samples were from 6 children with evidence of severe acute brain damage leading to death in 5 cases: i.e., 2 term newborns with perinatal asphyxia, a 4 week-old child with severe convulsions, a 3 year-old boy with hypoxia due to laryngitis, and a 12 year-old girl with encephalitis. One preterm baby survived severe hypoxia and developed hydrocephalus shortly afterwards. We conclude that BP becomes detectable in CSF of newborns and older children under certain pathological conditions, and that the presence of BP in CSF may be associated with severe brain tissue destruction.


A new defect of neutrophil chemotaxis and random motility in a child with recurrent bacterial infections and hyperimmunoglobulinemia E. A new defect of chemotaxis and random motility of polymorphonuclear leukocytes is described in a patient with severe recurrent bacterial infections since early childhood. This defect seems to be intrinsic to the cells. The patient's plasma did not contain an inhibitor of chemotaxis. Addition of plasma to the patient's cells restored their chemotactic activity. High concentrations of immunoglobulin E were found in the patient's plasma. Phagocytosis, bacterial killing, and reduction of nitroblue tetrazolium salt were normal. Histological examination of lung tissue revealed a pattern similar to that observed in chronic granulomatous disease.


Hyaline membrane disease: prognostic factors and medium-term follow-up. One hundred and twenty two cases of severe hyaline membrane disease are reported. 68 of them survived (57%). Adverse clinical, radiological and laboratory factors, and their effects on the early mortality rate, are analysed with particular reference to the referring centers, delay in admission, transport and the critical state of most infants on admission. The follow-up of 29 survivors treated before 1974 has been examined with reference to birthweight and assisted respiration. Four (30%) of the twelve infants with birthweights below 2000 g had major neurological sequelae. Only two out of the 17 babies with a birthweight over 2000 g had minor mental disturbances.


Prenatal diagnosis of beta-thalassemia using selective hemolysis of maternal cells contaminating fetal blood sample. The prenatal diagnosis of the severe, hereditary anemias may be impossible when a placental blood sample which contains a high percentage of maternal rather than fetal cells is obtained. An incubation system described by Boyer et al. [3] with minor modifications, was applied to mixtures of blood from prematures and adults in order to increase the proportion of premature cells. After 40 min incubation, 95% or more of adult red cells were destroyed, whereas 30-60% of premature red cells were recovered, as determined by several independent methods. In a pregnancy at risk for beta-thalassemia, a placental blood sample which was purely fetal was obtained. Complete lack of in vitro beta-globin synthesis showed the fetus to have homozygous beta-thalassemia. When fetal blood was mixed with maternal blood in a ratio of 1:15, beta-globin synthesis in the mixture was comparable to that of normal fetuses. In contrast, when the cell mixture was subjected to selective hemolysis prior to separation of globins, beta-globin synthesis again was not detectable. Thus, using selective hemolysis, the correct diagnosis could be established from a blood sample containing only about 6% of fetal cells.


Lipid peroxidation in platelets from patients with Spielmeyer-Vogt-Batten syndrome. Platelet lipid peroxidation was studied in normal controls, subjects with epilepsy and patients with the Spielmeyer-Vogt-Batten syndrome. The results showed wide intra- and inter-individual variation, particulary in the latter group. The mean value in Spielmeyer-Vogt-Batten syndrome was not significantly higher than the mean values for the other two groups.


Chronic mild diarrhoea, stunted growth and neuromuscular abnormalities. This report describes a 3 year-old girl with signs of ventricular hypertrophy, short stature, and persistent diarrhoea (without steatorrhoea or creatorrhoea) which was resistant to therapy. There was no clinical evidence of myopathy but a myopathic pattern was found on electromyography. Biochemical studies revealed no abnormalities. Routine histological studies of biopsied muscle showed no obvious structural abnormalities. Examination of 1 micrometer tissue sections revealed groups of atrophic fibers. Electronmicroscopy revealed widened spaces between the myofibrils with disruption of filament arrangement. The mitochondria in the motor end-plates were very distended and almost devoid of cristae.


Stimulus persistence in CFF: overarousal or underactivation? The physiological basis of hypothesized adult age increases in the persistence of stimuli was studied in 16 young (X age 19.1 years) and 16 old (X age 70.1 years) male and female subjects. Changes in CFF threshold and skin conductance were measured as a function of loud white noise activation and artificial pupil. CFF was significantly lower in the old group and with artificial pupil in both age groups. Significant effects were also found for activation x sex and activation x age x sex. Skin conductance change was significant for activation, activation x sex, artificial pupil x age, artificial pupil x order and artificial pupil x order x activation. The results were interpreted as supporting an overarousal basis of an age increase in stimulus persistence.


Aging and semantic memory: structural age differences. The objective of this research was to investigate age differences in the structure of semantic memory. The tasks employed (i.e., vocabulary, word fluency by conceptual category cueing and word fluency by initial consonant cueing) were representative of different age trends in quantitative test scores. Matching across age levels (young versus middle-aged) was in terms of family membership. Results showed a greater intra-individual variability and lower relationships between aspects of semantic memory by the time of middle-age. The results were viewed from process-oriented and environment-oriented explanatory perspectives.


Effect of chronic restraint on open field activity of aging C57BL/6N mice. Eight, 20, and 31 month old male C57BL/6N mice were exposed to three 24-hour restraint sessions per week, or to a nontreatment condition. All mice received five 2-minute open field tests after 5 and after 6 weeks of treatment. The activity of restrained mice tended to be greater than that of nonrestrained animals. In general, 8 month old mice were more active than older subjects. Age related activity decrements were prominent in the first series of open field tests, while restraint effects were most pronounced in the second series.


Effects of aging on monoamine oxidase activity of mouse and rabbit tissues. The effect of aging on the monoamine oxidase (MAO) activity in tissues of mice and rabbits was evaluated. There were no alterations in the MAO activity of liver, kidney, pancreas and brain (adult mice and rabbits) or testis and heart (adult mice) with aging. There were no alterations in the norepinephrine content of the brain, kidney and heart of older mice. The present study indicates that increased MAO activity is not inevitably associated with aging in all species.


Extracardiac malformations associated with congenital heart disease. The incidence of significant extracardiac malformations was determined in a combined clinical and autopsy study comprising 1000 infants and children with congenital heart disease treated and lost at the Children's Hospital in Helsinki. There were 567 boys and 433 girls. 1/4 of the children had a birthweight of 2500 g or less. 850 children were under 1 yr old. Death occurred during the 1st mth of life in 546 cases. Extracardiac malformations were encountered in 439 children. They were more common in girls than in boys. The incidence of associated malformations was comparatively high in infants with a low birthweight. The noncardiac anomalies were considered main causes of death in 1/3 of the cases. Extracardiac organs were involved in the following order of frequency: alimentary, skeletal, urogenital, central nervous and respiratory system. Of the main cardiac malformations, septal defects were associated with the highest and transposition of the great arteries with the lowest incidence of extracardiac anomalies. An accumulation of some defined noncardiac malformations was observed in patients with certain heart lesions.


Echocardiographic estimation of a left-to-right shunt in isolated ventricular septal defects. 35 infants and children with isolated ventricular septal defects (VSDs) had echocardiographic examination within 24 h of cardiac catheterization. Left atrial to aortic root (LA : Ao) ratio, left atrial internal dimension/meter square body surface area (LAID/m2) and left ventricular internal dimension in diastole/meter square body surface area (LVIDd/m2) were compared with the cardiac catheterization determined pulmonary-to-systemic flow (Qp : Qs) ratio. 35 children with normal cardiovascular findings served as controls. The LA : Ao ratio in the VSD group (1.38 +/- 0.13) was significantly higher than in the control group (1.01 +/- 0.05) (P less than 0.01). Similarly the LAID/m2 and LVIDd/m2 were significantly higher in the VSD group than in the control group (P less than 0.01). Additionally, echographic dimensions were increased in proportion to the elevation of Qp : Qs (r = 0.71--0.73). LA : Ao ratios higher than 1.4 : 1 were generally associated with Qp : Qs ratios greater than 2 : 1. All patients with Qp : Qs greater than 2 : 1 had LA : Ao ratios of 1.4 or higher. This study suggested that echocardiography is a useful noninvasive technique in estimating the Qp : Qs in patients with isolated VSDs, and may serve as an additional clinical parameter in the assessment of patients with VSDs.


Left anterior hemiblock in adult Africans. A total of 4,000 consecutive electrocardiograms covering an 8-yr period was studied and all cases with pure left anterior hemiblock reviewed on the basis of clinical diagnosis and subsequent follow-ups. There were 66 cases in all, representing 1.6% of the total series with an age range of 30--81 and a mean of 53.4 yr; 43 males to 23 females--a ratio of approximately 2 : 1. 34 cases (51.5%) were hypertensives all with a minimum diastolic pressure of 120 mm Hg before treatment. Congestive cardiomyopathy accounted for 16 cases (24.3%) and diabetes mellitus unassociated with other ailments for another 6 cases (9.1%). Other causes included mixed aortic valve disease with 2 cases (3%), endomyocardial fibrosis with 2 cases (3%). In 6 patients (9.1%), all above the age of 70, who had been admitted for minor surgical operations, no cause could be found. This etiological pattern differs from that seen in white populations where ischemic heart disease is by far the commonest cause. The extreme rarity to left anterior hemiblock in rheumatic mitral valve disease is considered of help in separating cases of lone rheumatic regurgitation from those of mitral regurgitation complicating congestive cardiomyopathy if and when diagnostic difficulty arises.


Successful surgical repair of double outlet right ventricle with situs inversus, l-loop, l-malposition and subaortic VSD in a 16-month-old patient. The case of a 16-mth-old patient who had double outlet right ventricle, l-loop and l-malposition in the presence of dextrocardia and situs inversus is presented. A successful repair was performed using an internal conduit to divert the blood from the left ventricle to the aorta. The outflow tract of the right ventricle was then enlarged with a dacron patch. The anatomic variations of double outlet right ventricle surgically corrected are reviewed.


Clinical and angio- and echocardiographic findings in 45 children with mitral valve prolapse syndrome. 45 patients with an age of 3--15.5 yr are reported. Only 9 of them showed symptoms (palpitations, dyspnea, fatigue). The murmur was often uncharacteristic, only 42% had a click. ECG changes could be found in 60%. The associated cardiac lesions and the angiographic findings are represented. Correlating to an angiocardiographically LVOTO we found in 13 patients (28.9%) the echocardiographic signs of an ASH with a septum/LV posterior wall quotient of 1.45 +/- 0.15. We conclude, that myocardial disease is one pathogenetic factor in the MVPS.


Direct measurement of myocadial hardness. Myocardial hardness, defined as resistance to a pitting force, was measured on several sites of the myocardium in 20 anesthetized dogs. The durometer used for hardness measurements consisted of an indentor, 4 mm in diameter, pressed perpendicularly on the myocardium by a calibrated spring (elastic modulus 325 N/m). Hardness changes during the cardiac cycle caused movement of the indentor which interrupted a light beam falling on a photoresistance. Changes in illumination of the photoresistance resulted in resistance changes, which were recorded using a Wheatstone bridge and a DC amplifier. Hardness was expressed in mm of spring shortenings. Balanced in (zero hardness), the indentor protruded 7.2 mm beyond the foot. Thus hardness adequate to press the indentor level with the foot defined as 7.2 mm. The left ventricular pressure (LVP) rise followed slightly the hardness rise (from 29.5 +/- 3.6 msec--mean +/- SEM--for the basal area at the right ventricle to 35.8 +/- 5.9 msec for the basal area of the left ventricle. Apical areas were significantly harder in systole than corresponding basal areas and left ventricular areas had a significantly higher systolic hardness (SH) than corresponding right ventricular areas. Changes in LVP by transfusion bleeding caused almost proportional changes in SH. While using a constant pressure reservoir in left atrium and another in aorta, adrenaline caused a significant increase in SH, decrease in diastolic hardness (DH) and increase in hardness width (WH); calcium chloride caused a nonsignificant increase in SH and WH and a significant decrease in DH; practolol caused a nonsignificant decrease in SH and a significant increase in DH and decrease in WH. Ligation of 3--5 branches of the anterior descending coronary artery resulted in a significant increase in DH and reduction in the WH distally to the ligation during the first 11 min. The WH was significantly reduced as a function of time in both areas (healthy and infarcted) taken collectively. The WH was significantly higher over the healthy area than over the infarcted one at corresponding times.


Potentiation of morphine hyperthermia in cats by pimozide and fluoxetine hydrochloride. Administration of morphine sulfate (1--4 mg/kg i.v.) to cats produces changes in body temperature, with hyperthermia appearing with larger doses. Since the central neurotransmitters dopamine and serotonin have been implicated in thermoregulation, studies were done to determine whether morphine's action could be mediated via these transmitters. Temperature responses were measured in freely moving cats by means of rectal thermometer probes. Either pimozide, 0.5 mg/kg i.p., a specific DA receptor blocker, or fluoxetine HCl, 10 mg/kg i.p., a specific inhibitor of 5-HT uptake, was administered 2--3 h prior to morphine injection. Temperatures were monitored for 3.5 h after morphine administration. Both agents were found to enhance the hyperthermic response to morphine with the maximum morphine effect occurring in most cases by 2 h. The results indicate that a balance in the ratio of 5-HT : DA may be involved in cat thermoregulation and that the hyperthermic response in the cat to morphine may be effected by shifting this 5-HT : DA ratio.


A comparison of the oximes HS-6 and HI-6 in the therapy of soman intoxication in rodents. The bisquaternary mono-oximes HS-6 and HI-6 may both be considered as potential therapeutic agents for soman intoxication. It has been found that HI-6 was superior to an equal dose of /S-6 in the treatment of soman intoxication in mice and rats. Not only did HI-6 protect against higher levels of soman, but also fewer "delayed deaths" were seen following HI-6. In anesthetized atropinized rats, the administration of HI-6 resulted in a longer duration of spontaneous breathing and a higher degree of recovery of neuromuscular function than did the use of HS-6. HS-6 interacted with soman to alter the rate of excretion of the oxime. This problem was not encountered when HI-6 was used.


Effects of adrenalectomy and adrenal steroids on norepinephrine synthesis and monamine oxidase activity. Rat heart norepinephrine (NE) tunover was increased 6--10 days after bilateral adrenalectomy. This increase was prevented by administration of deoxycorticosterone acetate (DOCA) but not by either hydrocortisone or corticosterone. Blood pressure decreased following adrenalectomy. This decrease was prevented by DOCA, hydrocortisone and corticosterone. Monoamine oxidase (MAO) activity increased in the heart but not in the liver following adrenalectomy. DOCA prevented the increase in heart MAO activity whereas hydrocortisone and corticosterone were ineffective. In intact animals, heart and liver MAO activity were not changed by 5 days of cold exposure, a procedure which increases NE turnover. It is suggested that the increase in heart NE turnover may be related to the increase in MAO activity seen after adrenalectomy.


A quantitative study of the calcium-magnesium antagonism in isolated strips of guinea-pig ileum. The effect of increasing magnesium concentration (0.61, 1.22, 2.44 and 4.88 mM) on the acetylcholine dose-response curve of isolated strips of the longitudinal muscle of the guinea pig ileum was studied qualitatively and quantitatively in Krebs solution with 2.55 and 5.10 mM calcium. The quantitative study was based on a hypothesis assuming the competition of both ions for a common binding site in the cell "stores" from which the calcium is mobilized following cholinergic receptor activation. The theoretical equations fit the experimental data and allow the calculation of the calcium and magnesium equilibrium constants. As a cross-check two groups of experiments were done to compare the influence on the acetylcholine dose-response curve of a gradual decrease of extracellular calcium either without or with magnesium. The amounts of magnesium used were those theoretically suitable for maintaining a constant amount of calcium in the hypothetical cell "stores". The results agreed with the predictions form the model proposed thus confirming both the hypothesis and the values obtained for the calcium and magnesium equilibrium constants.


Effects of benzodiazepines and pentobarbitone on the gaba-ergic recurrent inhibition of hippocampal neurons. The actions of benzodiazepines and pentobarbitone on GABA-mediated recurrent inhibition of hippocampal pyramidal neurons were investigated in the immobilized unanaesthetized cat. Extracellular action potentials of single neurons were recorded in regions CA1 or CA2 with 4 M NaCl-containing glass micropipettes. Bicuculline (0.1 mg/kg i.v.) reduced the period of inhibition induced by stimulation of the fimbria and the septum, but fludiazepam and diazepam (0.3--1.0 mg/kg i.v.) and pentobarbitone (15--30 mg/kg i.v.) prolonged the inhibition. The prolongation produced by these compounds was antagonized by the administration of bicuculline (0.3 mg/kg i.v.). The results suggest that these two classes of compounds potentiate GABA-mediated recurrent inhibition in hippocampal neurons in a similar way.


Single dose and cross tolerance studies of beta-phenethylamine, d-amphetamine and LSD in the chronic spinal dog. The effects of beta-phenethylamine (PEA), d-amphetamine and LSD were studied on spinal reflexes, autonomic signs, and behavior in the non-tolerant and LSD tolerant (30 microgram/kg/day) chronic spinal dog. LSD (10 microgram/kg) facilitated the flexor reflex, produced the stepping reflex, increased respiration, pulse rate and temperature, slightly dilated pupils and produced whining, tracking and restlessness. Direct tolerance developed to all of these effects except temperature. PEA (0.8 mg/kg/min infused for 12 min) and amphetamine (3.2 mg/kg) facilitated the flexor reflex, increased respiration, temperature and the skin twitch reflex latency, caused a marked mydriasis, retracted the nictitating membrane and produced restlessness and stereotypic head movements. PEA but not amphetamine elicited stepping, and only amphetamine consistently slowed heart rate. No cross tolerance to the physiologic or behavioral effects of amphetamine was observed. Partial tolerance developed only to the actions of PEA on the stepping reflex and the nictitating membrane. The single dose effects and the lack of cross tolerance to amphetamine and PEA suggest modes of action different from LSD. PEA has some actions which differ from those of amphetamine.


Effects of ouabain and potassium-free solution on the contraction of isolated blood vessels. Ouabain and K-free solution affected the tension development of isolated vessels as follows. In rabbit aorta, ouabain induced a transient contraction followed by a delayed sustained contraction whereas K-free solution was almost ineffective; both ouabain and K-free solution produced a sustained contraction in guinea pig aorta; rat aorta rarely responded to ouabain but developed a contraction in K-free solution. Phentolamine inhibited the transient contraction produced by ouabain in rabbit aorta. In rabbit aorta, ouabain produced a concentration-dependent potentiation of norepinephrine contraction. In denervated rabbit aorta, however, the potentiation only occurred in the presence of 5 X 10(-7) to 5 X 10(-6) M ouabain. K-free solution inhibited the norepinephrine contraction in denervated rabbit aorta. Ouabain potentiated the norepinephrine contraction in guinea pig aorta but not in rat aorta. It is concluded that ouabain and K-free solution affect contraction both indirectly via the release of endogenous catecholamines and directly by acting on vascular smooth muscle, and that there are species differences in the sensitivity to ouabain.


Mechanism of inhibition of renin release by clonidine in rats. In anaesthetized rats, the intracisternal injection of clonidine (1 microgram/kg) reduced mean arterial pressure (MAP), increased plasma renin concentration (PRC) while naphazoline (5 microgram/kg) was ineffective. The i.v. administration of clonidine (30 microgram/kg) still lowered MAP, but in this case, the drug decrease PRC, naphazoline (45 microgram/kg, i.v.) also reduced PRC. It is suggested that i.v. clonidine and naphazoline reduce renin release through activation of alpha-adrenoceptors within the kidney.


Muscimol antagonizes morphine hypermotility without potentiation of analgesia. Muscimol, a very potent and specific GABA agonist, strongly depressed characteristic morphine-induced locomotor activity. Muscimol induced only a very weak increase in the morphine analgesia measured in the hot plate test which perhaps could be a result of a freezing reaction. No effect on morphine analgesia was observed in the wire grid test. These results indicate that GABA differentially influences morphine stimulation and analgesia.


Characterization of the anti-stem cell activity of anti-mouse brain serum. The anti-stem cell activity of a high-titer rabbit anti-mouse brain serum preparation has been further characterized. Following absorption with bone marrow and erythrocytes the antiserum had dose-dependent cytotoxicity against pluripotent stem cells. Rigorous absorptions with bone marrow, spleen, liver, erythrocytes, and thymus failed to remove the anti-stem cell activity of the serum. Adult brain, the immunogen, but not neonatal brain, removed a substantial amount of the activity against stem cells. Maximal cytotoxicity occurred both with and without complement and was maximal following only a 4 degrees C incubation of cells with serum. The anti-stem cell activity was present in the serum globulin fraction. No increase in the frequency of microcolonies or, with longer growth periods, in splenic macrocolonies was observed, suggesting that CFU-s were completely inactivated by exposure to the antiserum. Injected antiserum also reduced CFU-s in vivo.


Studies on the inhibitory effect of granulocytes on human granulocytopoiesis in agar cultures. In the present study, the inhibitory effect of blood granulocytes on granulocytic colony formation from human white blood cells was tested. Attempts were made to clarify the effects of granulocytes by plating increasing numbers of polymorphonuclear cells (PMN) by using granulocytes which had been inactivated by freezing, by studying the effect of PMN removal and by observing the effect of dilution of granulocyte inhibitors to ineffective levels at different time intervals after the onset of culture. It will be shown that colony formation is inhibited by an excess of PMN and that the inhibitor is produced only by viable PMN. There is no inhibition during the early phase of the culture, thus suggesting that the CFU-C itself is not the target cell for the inhibition of colony formation in agar culture, but rather the more mature precursor cells of granulopoiesis.


The role of phagocytic cells in human blood leukocyte suspensions for in vitro colony-forming cells. The iron ingestion method was used to separate colony stimulating cells from in vitro colony forming cells (CFU-C) in human white blood cell (WBC) suspensions. The depletion of phagocytic cells (granulocytes and monocytes) from WBC eliminated spontaneous colony growth, without influencing the total number of CFU-C. Thus, phagocyte-free human WBC can be used as a target for measuring human colony stimulating activity (CSA). Such leukocytes can be cryopreserved, thus making possible the use of standardized target cell preparations for longitudinal studies. Hemolysate added to phagocyte-free blood leukocytes did not induce colony formation but could enhance it in the presence of a suitable CSA. Spontaneous colony formation of unseparated WBC was significantly reduced by selective destruction of granulocytes by freezing in 10% DMSO, thus indicating that both granulocytes and monocytes are involved in the production of endogenous CSA in WBC suspensions.


Increased granulocyte counts in recipients of plasma from leukapheresed rats: a dose response study. Humoral factors are elaborated by animal and human donors during filtration leukapheresis. Plasma obtained from rats after leukapheresis (PPP) increases granulocyte yields when given to donors prior to leukapheresis. In our studies, it appears that (1) the effect of PPP is dose-related, and (2) the granulocytosis and the titer of neutrophil releasing activity are proportional to the duration of leukapheresis. On the basis of our findings, we recommend initiation of clinical studies using postleukapheresis plasma to improve granulocyte harvests and that a dose of 1.5 ml of PPP/kg appears to be a reasonable starting point.


Cell kinetics of erythroid colony-forming cells (CFU-E) studied by hydroxyurea injections and sedimentation velocity profile. Cell kinetic characteristics of murine CFU-E were assessed by measuring femoral marrow CFU-E survival rates after injection of hydroxyurea at from 2 to 48 h before marrow collection. The results are compatible with the concept that the CFU-E represent a homogeneous non-selfsustaining population comprised of cells belonging to a single differentiation stage. Their cell cycle length was estimated to be 10 h. Marrow cells were also subjected to separation by velocity sedimentation, and the effect of preceding hydroxyurea injections on the distribution profile of CFU-E was ascertained. Variations in cell size of CFU-E were interpreted to represent CFU-E in various phases of their cell cycle. CFU-E in either G1, S or G2 at the time of their removal from the marrow were capable of forming erythroid colonies in vitro, but it appears that the CFU-E lost this capacity after completing their cell cycle within the marrow of the intact mouse.


Stimulatory effects of products from inflammatory exudates upon stem cell production. The present study is based on the hypothesis that a humoral agent produced in inflammatory exudates is transported to the bone marrow where it stimulates CFU-S to differentiate into leukocytic precursors. Inflammatory exudates were produced by the subcutaneous implantation of a sterile acrylic cup filled with bacteria-free Hanks' balanced salt solution (HBSS) into B6D2F1 mice. The cups were removed 24 h later and the cells were separated from the supernatant. Cells collected from individual mice were pooled, as was the supernatant. Thereafter, normal mice received via tail vein either exudate cells, supernatant, plasma from cup-implanted or from normal mice, bone marrow cells or splenic cells from normal animals or HBSS. Another 24 h later bone marrow was removed from all mice and injected into previously lethally irradiated mice or suspended in vitro in agar-supported media. Nine days later the mice were euthanatized, the spleens removed, and colonies (CFU-S) counted. At the same time, colonies (CFU-C) were enumerated from the agar plates. The results clearly indicate that the bone marrow obtained from mice stimulated with either exudate cells or with super-natant or plasma obtained from cup-implanted mice contained a significantly greater number of CFU-S and CFU-C than did any one of the four control groups. These findings appear to substantiate the hypothesis.


Multiple branching of cerebellar efferent projections in cats. The retrograde labeling of neurons in the deep cerebellar nuclei with horseradish peroxidase was used to compare the morphological characteristics of neurons in the dentate and interposed nuclei projecting in the cerebellothalamic, cerebello-olivary, and cerebellar nucleocortical pathways. The results from these studies demonstrated that cerebellothalamic and nucleocortical projections from the dentate and interposed nuclei originate from similar populations of spindle- and multipolar-shaped neurons with somal diameters throughout the range of cells present in the deep nuclei. However, only spindle-shaped neurons with somal diameters of 9--15 microns project in the cerebello-olivary pathway. From these anatomical studies, it was concluded that some of the neurons in the dentate and interposed nuclei which project to the thalamus, inferior olive, and cerebellar cortex have similar morphological characteristics. Electrophysiological experiments were carried out to investigate whether or not some of these neurons project to all three sites viaaxon collaterals. From stimulus sites in the thalamus, inferior olive, and cerebellar cortex, numerous neurons were antidromically activated in the cerebellar nuclei. Collision experiments between these antidromic responses confirmed that single neurons projected to all three of these sites. These studies therefore demonstrate that the axons of some neurons in the dentate and interposed nuclei have collateral branches in both the ascending and descending limbs of the brachium conjunctivum as well as in the cerebellar nucleocortical pathway. Functional implications of the collateral branching of cerebellar efferent projections are discussed.


Studies on the regulation of RNA synthesis in neuronal and glial nuclei isolated from rat brain. In searching for regulatory mechanisms involved in the cell-specific neuronal and glial transcription a cell-free transcriptional system has been developed using neuronal and glial rat brain chromatin and partially purified neuronal and glial nuclear rat brain RNA polymerases. Both free and chromatin-bound (engaged) neuronal and glial RNA polymerase fractions were separated from isolated neuronal and glial rat brain nuclei to determine their transcriptive efficiency. A double number of RNA initiation sites was measured on the neuronal when compared to the glial chromatin, independently of whether the neuronal or the glial RNA polymerase preparation was used for the determination. Structural modification of the neuronal and glial chromatin template by acetylation with acetyl-coenzyme A leads to an increase of the total number of RNA initiation sites available for exogenously added rat brain RNA polymerase. This indicates that acetylation of chromatin-bound proteins is capable to render primarily restricted gene sequences transcriptable. A positive correlation exists between the extent of acetate uptake by neuronal and glial chromatin-bound histone fractions and the extent of the increase of the number of RNA initiation sites is specifically related to histone acetylation rather than to acetylation of any other chromatin protein. Significant information in this respect could be achieved by dissociation of chromatin into its principal components and selectively reconstituting DNA with specifically acetylated histone and non-histone proteins.


Collinearity tolerance of cells in areas 17 and 18 of the cat's visual cortex: relative sensitivity to straight lines and chevrons. Collinearity tolerance and length dependence of orientation tuning were compared in cells recorded from areas 17 and 18 of the lightly anaesthetised cat's visual cortex. Orientation tuning and interaction between receptive field halves of the same cells are reported in the preceding paper and elsewhere (Hammond and Andrews, 1978a, b). In confirmation of previous work, increase in stimulus length was associated with sharper orientation tuning in all simple and hypercomplex cells, and in most complex cells even in the absence of length summation. Cells in areas 17 and 18 were more sharply tuned for chevrons was noticeably skewed compared with tuning for straight lines. In area 17, the best response was always obtained with a straight line of optimal orientation. The two halves of the receptive fields of some cells in area 18 had dissimilar preferred orientations. Even in cells whose receptive field halves were similarly tuned, broadly tuned, or apparently untuned for orientation, simultaneous stimulation of both halves of the receptive field led to substantial sharpening of tuning. In cells with dissimilarly tuned half fields, the skew in chevron tuning was predictable from the orientation tuning of each half of the receptive field. Two area 18 cells responded consistently better to a chevron stimulus than to a straight line of any orientation.


Orientation tuning of cells in areas 17 and 18 of the cat's visual cortex. Sharpness and symmetry of orientation tuning were quantitatively investigated and compared in ninety-seven cells from areas 17 and 18 of the lightly-anaesthetised feline visual cortex. Halfwidths of orientation tuning at half-height ranged between 5 degrees and 73 degrees for long stimuli, with an extreme exception at 111 degrees (excluding untuned cells). There was a tendency for cells in area 18 to be more broadly tuned than those in area 17, due largely to the relatively sharp tuning of area 17 simple cells. Confirming previous work, simple cells were more sharply tuned than complex cells in area 17. In area 18, there was no clear distinction in sharpness of tuning between complex type 1 cells (equated with area 17 simple cells), complex type 2 cells (equated with area 17 complex cells), or hypercomplex cells. Approximately 60% of cells in both areas were asymmetrically tuned for orientation: ratios of half-widths to either side of the optimal orientation ranged from 1.0-3.0, exceptionally 5.8. Asymmetry of tuning was more marked in area 18 than in area 17, except that area 18 complex type 2 cells as a group were relatively symmetrically tuned for orientation. Occasional cells with different preferred orientations for opposite directions of motion, for each peak of a bimodal response to a single direction, or for each half of the receptive field were also observed. The latter are described in the following paper.


Behavior and electrical brain stimulation in the green iguana, Iguana iguana L. II. Stimulation effects. Behavioral responses were electrically elicited in the brains of 21 green iguanas. At 518 stimulation sites, a limited number of behaviors could be reliably elicited. Except for some motor responses which had a forced appearance, they corresponded to the basic activity of green iguanas, exploratory behavior, display, defensive and escape-related behavior. Head-nodding displays were reliably elicited post stimulation when imminent escape was prevented experimentally but rarely during stimulation. Goal-directed behavior, i.e., feeding, drinking, mating and fighting behavior, were not elicited. The stimulation sites of frequently elicited behavioral responses revealed regional differences and some structural correlations. The majority of sites yielding defensive display responses were found in the hypothalamus, while dewlap display was more readily and widely elicited. Axial rotation and head-raising were elicited in a ventrothalamic zone extending into the tegmentum mesencephali. Tongue-flicking response sites were mostly concentrated in ventromedial areas of the tel-, di- and mesencephalon. Most escape-related responses were distributed unspecifically but the sites of violent flight responses were confined to the dorsal and lateral mesencephalon.


Changes in pattern discrimination learning induced by visual deprivation in normal and commissurotomized pigeons. The effect of monocular (MD), binocular (BD) and alternating monocular (AMD) deprivation on monocular pattern discrimination learning and interocular transfer was investigated in pigeons reared with intact and sectioned supraoptic decussation (DSO). In BD and AMD animals acquisition and interocular transfer of two different pattern discrimination problems remained as good as in the control animals (CO). Monocularly deprived animals (MDE) required significantly more trials to learn the discriminations through the deprived eye, when it was trained first, and interocular transfer from the deprived to the experienced eye was absent. However, if the experienced eye was trained first (MED), learning with the deprived eye was at least as rapid as with the experienced eye. This indicates positive interocular transfer from the experienced to the deprived eye. Interocular transfer of pattern discriminations was completely blocked by section of the DSO in both adults (DSOad) and newly hatched animals (DSOjuv). The elimination of binocular interaction by commissurotomy from the beginning of the postnatal life failed to produce an impaired pattern discrimination learning in monocularly deprived animals.(MD+DSO). The results are discussed in terms of competition between the projections from both eyes in the visual Wulst.


Responses of cerebellar units to a passive movement in the decerebrate cat. The responses of mossy fibers (MF), granular cells (GrC) and Purkinje cells (PC) were recorded in the cerebellum of the decerebrate cat during a passive movement about the forepaw wrist joint. Three main discharge patterns containing information about all the static and dynamic parameters of the movement were found. Simultaneous recording of complex spikes (CS) and simple spikes (SS) showed that the activity of PC can be modulated through either MF or CF input channels alone or both together. In the latter case SS and CS discharge most commonly showed an opposite behavior, in which the increase of the frequency of one type of spike was accompanied by a decrease of the frequency of the other type. Both inputs displayed tonic and phasic characteristics and all the qualitative discharge patterns observed. Therefore it was concluded that aside from differences in the discharge frequency, both inputs are able to directly signal peripheral events.


Ultrastructure of the anterior ventral and anterior medial nuclei of the cat thalamus. Electron microscopical studies of the thalamic AV-AM nuclei substantiated the presence of two main types of neurons, i.e. principal (or relay) cells and Golgi type II interneurons. Characteristic synaptic islands are found in abundance in the AV-AM. Four different types of synaptic terminals have been identified in these islands: RL-boutons = large axonal terminals with round synaptic vesicles; RS-boutons = small axonal terminals with round synaptic vesicles; F1-boutons = small axonal profiles containing flattened synaptic vesicles, and F2-profiles interpreted as presynaptic dendrite appendages, bearing pleomorphic vesicles, both belonging to the Golgi type II interneurons. --The synaptic relations were studied in normal preparations and after lesions in the mamillary body, limbic cortex and hippocampus. The specific afferents (RL-boutons)--originating from the medial mamillary nucleus--are presynaptic to both relay cell dendrites and "presynaptic" dendrite profiles of Golgi type II interneurons, which in turn are presynaptic to the same relay dendrites (synaptic triads). RS-boutons originate mainly from limbic cortex and hippocampus.


Visual orientation in the rat: a dissociation of deficits following cortical and collicular lesions. Rats with either bilateral ablations of superior colliculus, bilateral ablations of visual cortex, or sham operations were trained to run across a large arena towards a small illuminated target which varied in location from trial to trial. An impairment in this visually-guided running was apparent in the cortical group, but not in the collicular group. When, in a second experiment, the spatial relationships within the apparatus were changed by extending the entry-tunnel some distance into the arena, the running of the cortical group became even more impaired, while the collicular animals continued to run towards the targets under efficient visual control. In a third experiment, the effect of introducing a novel flashing light in various locations around the perimeter of the arena was investigated. It was found that unlike the other two groups, the collicular animals showed no orienting reflex to the novel stimulus when it was presented outside a broad central area of the visual field.


Endometrial morphology of women using a d-norgestrel-releasing intrauterine device. Endometrial biopsies were obtained from 12 volunteers treated with d-norgestrel-releasing intrauterine devices (IUDs) with two different release rate. Four subjects scheduled for hysterectomy had d-norgestrel-releasing IUDs inserted approximately 1 month prior to surgery. The effect of d-norgestrel on the endometrium and fallopian tubes of the removed uteri was examined. A uniform suppression of the endometrium with glandular atrophy and decidualization of the stroma was found in all of the endometrial specimens. Moreover, changes similar to those observed during the luteal phase and early pregnancy could be seen in the tubal epithelium.


Evolution of the properties of semen immediately following vasectomy. Semen parameters were analyzed in a series of 76 men pre- and postvasectomy. The mean volume decrease was 0.66 ml but it was 0.5 ml or more for only 53% of subjects. A decrease in the number of spermatozoa was correlated primarily with the number of ejaculations. In nearly all cases the total number of spermatozoa contained in all semen samples examined after vasectomy was clearly lower than the average number contained in only one ejaculation prior to vasectomy. Motile spermatozoa were never observed after the 15th day following vasectomy. The reappearance of motile spermatozoa after that time was an almost certain sign of a defect in the vas block or of recanalization of the vas deferens.


Role of androgenic hyperactivity in anovulation. In the course of an investigation of 60 patients with clomiphene-resistant anovulation, 35 cases of androgenic hyperacitvity were detected. Fractionation of urinary 17-ketosteroids (17-KS) by a rapid method of chromatography proved to be both practical and reliable for the detection and classification of androgenic disorders of adrenal, ovarian, or mixed origin. In contrast to the total 17-KS values, the fractionated 17-KS values were elevated in all but one of these cases. Following dexamethasone suppression, individual 17-KS showed significant decreases in both adrenal and mixed adrenal-ovarian cases, in contrast to ovarian cases in which no significant change was detected. Human chorionic gonadotropin (HCG) stimulation combined with dexamethasone suppression did not cause any significant change in individual 17-KS values in the adrenal group, whereas both the mixed adrenal-ovarian and ovarian cases showed significant increases. Of 34 treated patients, 22 conceived, 21 had normal deliveries, and 1 aborted. Twelve became ovulatory. Eleven patients were treated with dexamethasone, nineteen with combined dexamethasone and clomiphene, two with dexamethasone and HCG, and two with HCG only.


Nitrofurazone: vas irrigation as an adjunct in vasectomy. Intraoperative vas irrigation with nitrofurazone utilized in a 1-mg/ml concentration can cause immediate sterility postoperatively. This irrigation procedure adds little time to the standard vasectomy and can easily be performed as an outpatient office procedure, minimizing time-consuming postoperative semen analyses. Moreover, in developing countries where postoperative vasectomy follow-up may be more difficult to obtain and may even be nonexistent, this procedure would provide an additional positive factor in an attempt to ensure sterility.


Prevention of peritoneal adhesions by the combined use of spongostan and 32% dextran 70: an experimental study in pigs. Twenty female pigs underwent laparotomy during which transection of both uterine horns and wedge resection of both ovaries were performed with a standard technique. Following the injuries a mixture of Spongostan and 32% dextran 70 was applied only to the lesions on the right side. Three weeks after surgery another laparotomy was performed and the degree of adhesion formation was recorded. A marked reduction in degree and extent of adhesions was observed on the treated side as compared with the control side. The possible advantages of a compound that can be applied locally and has hemostatic properties as well are discussed.


Prevention of pregnancy in rabbits using vaginal application of prostaglandin f2alpha. Seventy-two rabbits were artificially inseminated at the time of ovulation induced by intravenous human chorionic gonadotropin. Twenty-four hours later vaginal suppositories containing graded amounts of prostaglandin F2alpha (PGF2alpha) (5 to 25 mg) were inserted into test rabbits in each group. A control group received plain vaginal suppositories. Ten days later the rabbits were killed and examined for numbers of corpora lutea and implantation sites. The results indicate that 5 to 15 mg of PGF2alpha had no effect or a minimal effect on the number of implantation sites, that 20 mg of PGF2alpha reduced the number of implantation sites, and that 25 mg of PGF2alpha was the most effective dose. Fifteen of twenty treated rabbits were not pregnant, despite the presence of ovarian corpora lutea. Four remaining rabbits were pregnant but had markedly reduced implantation sites (four, two, three, and two fetuses, respectively. PGF2alpha is known to increase tubal motility markedly. These data are consistent with such a mechanism's inhibiting pregnancy when used postcoitally in rabbits.


[Factorial analysis of evoked brain potentials]. The method of main components aided to study the changes of EPs led from different brain structures during action of drugs on synaptic organizations of the brain. Two factors were singled out: the unspecific one comprised late components of EPs led from such structures as caudate nucleus, black substance; the specific factor united the components of EPs associated with the visual projection system and the initial component of EP in CA-1 field of the hippocampus. The weight coefficients of these two groups of components of EPs changed in different ways under the effect of drugs: the drugs different by their synaptic action exerted opposite effects upon distribution of the weight coefficients over the EP components under study.