[Ultrastructural diagnostic problems of pleural tumors. A study of 125 cases (author's transl)]. Ultrastructural studies may improve the diagnosis of pleural tumors. A comparative study of 125 primary and secondary pleural cancers provided the major structural features needed for differential diagnosis. Two cell types were always present in malignant mesothelioma: differentiated mesothelial, and fibroblastoid cells. The former had some features of metastatic epitheliomas (microvilli, microfilaments, junctional complexes, basement membranes). The later were specific. They were sometimes isolated, had the general aspect of fibroblasts but possessed typical microvilli. It was difficult to assess the diagnosis of malignant mesothelioma on isolated differentiated mesothelial cells in pleural fluids or biopsies. Cilia or secretory granules were found only in metastatic cells. The finding of fibroblastoid cells in a pleural tumor proves its mesothelial origin.


Prenatal stress reduces fertility and fecundity in female offspring. Female rats subjected to prenatal stress later experienced fewer conceptions, more spontaneous abortions and vaginal hemorrhaging, longer pregnancies, and fewer viable young than nonstressed rats. The offspring of the prenatally stressed rats were lighter in weight and less likely to survive the neonatal period. Prenatal stress may influence the balance of adrenal and gonadal hormones during a critical stage of fetal hypothalamic differentiation, thereby producing a variety of reproductive dysfunctions in adulthood.


Release of luteinizing hormone in male mice during exposure to females: habituation of the response. Male mice release luteinizing hormone when exposed for a short time to a female. In this experiment, multiple blood samples were withdrawn by atrial cannulas from tethered males during either continuous or intermittent exposure to nonreceptive females. After an immediate, transient release of luteinizing hormone, continuous exposure to the same female was accompanied by only random, spontaneous elevations in plasma levels of this hormone. Successive presentations of the same female at 2-hour intervals elicited gradually diminishing luteinizing hormone responses. Exposing such unresponsive males to novel, diestrous females, however, dramatically stimulated their release of the hormone. These results demonstrate habituation of a socially induced, neuroendocrine response involving reproductive hormones.


Comparison of dairy cows with low or high rate of udder infection. Within farms, animals with low and high rate of udder infection were selected from data of a mastitis-prevention field experiment during 3.5 years. Differences between the groups in udder conformation and milkability appeared to be small but were consistently to the disadvantage of the high infection rate group. In the course of a least three preceding lactations the percentage of quarters infected at any time was 53 per cent in the low and 91 per cent in the high infection rate group. The number of infections per quarter infected was 1.53 for the low infection rate group and 2.53 for the high infection rate group. As compared with infection-free quarters it was shown that the duration of infections with udder pathogens was significantly shortened if a quarter was already infected with secondary, i.e. less or non-pathogenic, bacteria. It was not possible to demonstrate differences in cell count or immunoglobulin levels in infection-free quarters between the low and high infection rate groups.


The endocrine background of human renal cell carcinoma. III. Role of inhibitors of R 5020 binding in tumour cytosol. Cytosol preparations obtained from 9 different human renal cell carcinomas were investigated for the eventual presence of progestin-binding inhibitors which might offer an explanation for the previous failure to demonstrate high receptor levels in the tumour tissue. The inhibitory potency of these preparations was estimated by measuring the decrease of R 5020 binding to uterine progestin receptors in the presence of tumour cytosol. Interestingly, cytosol from human renal cell carcinoma was found to contain progestin-binding inhibitors. The average inhibition of R-5020-receptor interaction amounted to 46%. In only 1 out of 9 cases, binding was completely suppressed. In order to circumvent the inhibitory reaction potentially occurring in cell-free systems, R-5020-binding studies additionally were performed in cell suspension. Out of 7 carcinomas studied using this assay system, 5 did not contain any specific progestin-binding entities. In 1 tumour, receptor-atypical non-saturable binding was observed. Only in isolated cells prepared from 1 other carcinoma, could slight indications for the presence of low concentrations of progestin receptors be detected.


A test for bladder neck competence: the fluid bridge test. The momentary entry of urine into the proximal urethra during coughing can be demonstrated by a new test which can be conducted using apparatus now commonly available for urodynamic investigations. If the bladder neck opens, a fluid bridge is established between points of pressure measurement in the bladder and in the proximal urethra. Thus, the pressures at these two points momentarily become equal. The clinical value and relevance to physiology may not become clear for some time, but the relatively simple apparatus and procedure, and the ease with which the results can be translated into physical facts, provide important advantages over other dynamic tests of the urethra which are currently possible.


[Two rare congenital malformations of the female urethra]. Two cases of incontinent females due to malformations of the dorsal wall of the urethra are presented and surgical corrections are discribed. The causal factors for the development of the malformations are explained by irregularities of the Wolffian ducts' regression during the transition period between in gonadal development between the 3rd and 5th week of gestation. The new medical technical term "indifference-syndrome" is proposed, to distuingish these malformations of the female urethra from true hypospadia.


Patient costs for urodynamic testing.

Patient costs for urodynamic testing. Urodynamic investigations are not completely standardized. However, the number of exhibits of urodynamic equipment at urologic meetings by commercial firms suggests that these studies have considerable applicability and relevance to everyday practice. Investment by a urologist in equipment for urodynamic testing should be cautious in the light of the costs for these investigations reported from centers in Canada, the United States, and Western Europe. The figures suggest that sophisticated urodynamic testing is not a screening test -- it is too expensive, but large urodynamic laboratories appear to charge only for a portion of the actual cost of such testing. Since urodynamic testing is much more expensive than actual patient charges, it is probably not yet cost effective in its present state of development.


Effect of drugs on progesterone metabolism in the female rat. Various drugs brought about a reduction of serum progesterone level irrespective of whether or not a potent inducer (phenobarbital, 4-methyl-coumarin) or a hepatotoxin (carbon tetrachloride, alpha-naphthylisothiocyanate, coumarin) has been administered. The decrease by hepatotoxins was highly significant during the estrus phase of the cycle. These treatments affected the hepatic level of progesterone and altered the uptake of [4-14C]progesterone in vivo. The serum level of progesterone was significantly decreased by phenobarbital and carbon tetrachloride; however, the incorporation into the liver was enhanced by phenobarbital and reduced by carbon tetrachloride. This opposing hepatic action showed selectivity; phenobarbital increased the oxidative pathway of progesterone metabolism (formation of 6 beta-, 16 alpha-, 20 alpha-hydroxyprogesterone) but the reductive pathway remained unaltered (formation of pregnanediol, pregnanolone). Conversely, carbon tetrachloride diminished oxidation and raised reduction of progesterone. These results have been confirmed by measurements of progesterone metabolism in vitro using isolated microsomes. Phenobarbital brought about an induction of progesterone 16 alpha-, 6 beta- and 20 alpha-hydroxylase, did not affect progesterone delta 4-5 alpha-dehydrogenase, whereas carbon tetrachloride inhibited hydroxylase and raised dehydrogenase activities. The action of these test compounds on serum and liver levels of progesterone and on the variation of progesterone metabolism seemed to be related to changes manifest in the function of the hepatic endoplasmic reticulum. Similar changes might be associated with the development of mild hepatic lesions induced by various steroids.


Clinical effect and metabolism of S-sulfonated immunoglobulin in 7 patients with congenital humoral immunodeficiency. 7 patients with primary humoral immunodeficiency were given an S-sulfonated IgG preparation, 100 mg/kg i.v. at intervals of 3--4 weeks, for treatment of, or prophylaxis  against, infection. The clinical effects and metabolism of S-sulfonated IgG were studied. No side reactions attributable to S-sulfonated IgG occurred in any of the patients. The S-sulfonated IgG was completely transformed into intact IgG within 24 h after administration, and had a mean half-life of 21 days, comparable to that of intact IgG. Complete restoration of IgG Fc fragment activity occurred within 24 h following injection, as assessed by reversed passive cutaneous anaphylaxis.


Posttransfusional immunologic thrombocytopenia. A case report. A case of posttransfusional immunologic thrombocytopenia is reported in a 75-year-od PlA1-negative woman. This was the second episode of postoperative and posttransfusion thrombocytopenia in the same patient who had had only one pregnancy. Both thrombocytopenic episodes were subclinical and discovered by systematical hematologic study. A potent anti-PlA1-antibody (titer 1/128) was demonstrated by the platelet-indirect radioactive Coombs test which appeared more sensitive than other platelet immunological assays used. The very long duration of the thrombocytopenia is discussed as well as the therapeutic possibilities in such cases.


Studies on the embryogenesis of the tapeworm Cittotaenia variabilis (Stiles, 1895) using transmission and scanning electron microscopy. The embryogenesis of the tapeworm Cittotaenia variabilis from the oocyte to the oncosphere is followed using scanning electron microscopy (SEM) in conjunction with ethanol cryofracture. Transmission electron micrographs and histochemistry are used to corroborate the inferences drawn from the SEM studies. Evidence is given for oocyte granules, the uterine epithelium, and the outer envelope as sources of components for the outer capsule. The contributions and senescence of the inner envelope and its relationship to the embryophore are given.


The contents of water-insoluble dietary fibre in finnish berries and mushrooms. A preliminary study. The contents of water-insoluble dietary fibre were estimated in Finnish berries and mushrooms. The contents in berries varied from 8.9 to 26.6% in dry matter and in mushrooms from 19.6 to 41.6 in dry matter.


Maternal behavior in the primiparous and multiparous golden hamster. Changes in the normal behavior patterns seen during lactation in the female golden hamster have received relatively little attention in the past (Rowell 1961; Daly 1972). The purpose of this experiment was to characterize and compare maternal behavior in female hamsters during gestation and 24 days of lactation, with their first and second litters. Each was observed for 1/2 h daily, and her behavior recorded every 10 s. Maternal behavior decreased over time in the mothers during both first and second lactations, while "non-maternal" behavior increased. No differences were observed in these measures between the first and second lactation.


[Stability of the cardiovascular functions of different genetic strains of rats subjected to emotional stress]. The level of catecholamines was measured in various brain parts in rats of August and Wistar lines, characterized by different stability of cardio-vascular functions in emotional stress. In norm, the August line has a higher content of dopamine (DA), in the mid-brain in particular; the Wistar line has a higher content of noradrenaline (NA) in the hypothalamus. In susceptible animals, which showed different cardio-vascular disorders during 30 hours of immobilization (48% of the Wistar line and 90% of the August), and in animals resistent against emotional stress, the changes in the initial level of catecholamines were observed, both common and specific for two lines. An assumption is made that the stability of cardio-vascular functions in the emotional stress is provided for by an intensive metabolism of the NA-synthesizing neurones in the brain isthmus, and by a moderate activity of the DA-synthesizing neurones of the mid-brain; the susceptibility to cardio-vascular disorders in the emotional stress is due to increase in the activity of the DA-synthesizing mid-brain neurones, the decrease in the activity of the DA-hydroxilase and the exhaustion of NA in the hypothalamus.


Preparation and properties of pectic enzymes produced by Trichoderma lignorum. Polygalacturonase and protein-methylesterase were isolated from shaken culture of Trichoderma lignorium. Isolation was carried out with various agents. Methanol was the most suitable precipitant for isolating polygalacturonase, yielding enzyme preparations 6.6 times more active than that of culture filtrate. Likewise, tannin afforded active fractions at pH 4 and 0.05% concentrations. Similarly, 50% ammonium sulphate saturation gave active fractions. The least polygalacturonase activity was obtained from ethanol. In any of the organic solvents used, highest enzymic activity was obtained when using only one volume. As regards pectin-methylesterase, no correlation existed between its activity and concentration of the precipitant used. A substrate concentration above 0.8% was a limiting factor for polygalacturonase activity, while optimum enzyme concentration was 40 microgram protein/ml at 40 degrees C and pH 4.45.


[Increased tolerance of the dopamine- and serotoninergic systems during chronic administration of haloperidol and levomepromazine]. In experiments on male albino rats single administration of haloperidol produced catalepsy, increase in dopamine turnover, enhancement of main dopamine metabolite homovanilinic acid in the forebrain. After single administration of the levomepromazine the cataleptogenic effect was accompanied by an enhanced 5-hydroxyindole acetic acid level, and no influence on the dopamine metabolism was observed. During chronic administration of haloperidol and levomepromazine their ability to induce catalepsy and to increase homovanilinic acid or 5-hydroxyindoleacetic acid concentration diminished. Thus, it appears that chronic administration of haloperidol reduces the sensitivity of dopamine receptors, and chronic administration of levomepromazine--reduces the sensitivity of dopamine and serotonin receptors in the brain.


[Psychoneurologic status of preschool children who have sustained hyperbilirubinemia during the newborn period]. A study of the neurological and mental state (as well as of the functional state of some system) with the aid of EMG, REG and EEG in 110 children permitted the authors to conclude that the residual period of hyperbilirubinemia is characterized by a morphofunctional brain immaturity. Clinically it may be expressed in frequent vegetovascular disorders and different psychopathological syndromes, decreasing the adaptational possibilities of the functional systems and disturbing the social adjustment of children. The residual period of hyperbilirubinemia of the newborn is being considered as a period of a relatively favourable and unstable compensation. The authors recommend a certain system of organizational, pedagogical and medical measures ensuring mental and physical health of these children.


[Pathogenesis of stereotyped behavior].

[Pathogenesis of stereotyped behavior]. The paper concerns the syndrome of stereotyped behaviour in rats induced by disturbance of inhibition in both caudate nuclei under influence of tetanus toxin, penicillin, and pirotoxin injected in these nuclei. Stereotyped behaviour could be inhibited by administration of GABA into the same brain area, as well as by a systemic administration of haloperidol, diazepam, aminalon, and lithium chloride. The conclusion is made that the disturbance of GABA-egric control in the caudate nucleus is a significant pathogenetic condition of the hyperactive neostriar dofaminergic apparatus, appearing due to disinhibition. Both links compose the pathogenetic basis of the syndrome of stereotyped behaviour.


[Changes in innate forms of motor behavior in rats during long-term hypokinesia]. The structure of motor behaviour in response to environmental tests--"open field" and "with-a-partner" situation (according to P. V. Simonov)--was studied in rats after 1, 3 and 6 weeks of hypokinesis, (to K. Hecht), as compared to the control. In control animals a relatively low level of orienting-investigation reactions and of grooming was observed as well as a low alimentary activity, which is considered as a manifestation of innate passive defensive reactions in the above situations. Disappearance of these reactions in the course of hypokinesia has two stages: predominant increase in orienting-investigating reactions (1-3 weeks); their subsequent decrease and an increase in the grooming (after 6 weeks). The relation between innate and conditioned behavioural changes is discussed as well as stability of alimentary behaviour in rats.


Purification of cobalt-activated acylase by affinity chromatography. alpha-Hydroxyisocaproyltyrosine (HyIc-Tyr-OH), a potent competitive inhibitor of the cobalt-activated acylase form 2, was synthesized. Its derivative, alpha-aminopentyl-HyIc-Tyr-OEt was coupled to cyanogen bromide-activated Sepharose 4B and was used for about 100-fold purification of the acylase from human liver by affinity chromatography. The preparation obtained did not show aminoacylase, aspartyl acylase or alanylarylamidase activities. The same chromatographic method was also applied to isolate form 2 of the serum acylase from patients with viral hepatitis and guinea pig placenta.


Prostaglandin-stimulated LH release in cyclic and ovariectomized rats. The ability of prostaglandin (PG) E2 treatment to stimulate luteinizing hormone (LH) release was compared in cyclic (4-day) and ovariectomized rats. PGE2 (500 micrograms) was injected sc and plasma LH concentration was determined in serial jugular blood samples. Administration of PGE2 at 13.30 h on each day of the oestrous cycle resulted in a significantly greater increase in plasma LH levels at pro-oestrus and oestrus than at dioestrus 1 and 2. This differential response by the hypothalamo-hypophyseal axis during the oestrous cycle implicates regulatory activity by ovarian steroid feedback. In oestrogen-primed ovariectomized rats, PGE2 administration stimulated a significant increase in plasma LH, but similar treatment in non-primed castrates decreased plasma LH levels. This finding suggests a major role for oestrogen in regulating this response.


Twenty-four hour sleep-wake pattern of plasma LH in patients with anorexia nervosa. The 24-h sleep-wake pattern of plasma LH was studied in 18 patients with severe weight loss. Sixteen patients had anorexia nervosa, one suffered from schizophrenia and one had a gastric ulcer. The age of the patients ranged from 13 to 31 years. Seventeen women and one boy participated in the study. Their weight ranged from 51 to 73% of the ideal body weight (IBW) at the first 24-h study which was at one week after admission to the hospital. Blood was taken through an indwelling venous catheter every 30 min. The patients' weight increased under behavioural therapy and they were re-studied when they had gained approximately 10% IBW and again prior to release from the psychiatric ward. The LH patterns were classified as infantile, pubertal or adult. All patients except for two had an infantile pattern at the first study. Except for the two patients who had no anorexia nervosa, all developed a pubertal and/or an adult pattern. All patients whose weight was below 69% IBW had an infantile LH pattern. All patients whose weight was below 69% IBW had an infantile LH pattern. Adult patterns were only seen when the body weight was greater than 80% IBW. The increase of the average 24-h LH values was slower the older the patients were and the longer they had been anorectic.


Immune thrombocytolytic purpura (ITP): a diagnostic and therapeutic survey of 86 cases with regard to the results of splenectomy and conservative therapy. The therapeutic results in 86 cases of ITP seen over a period of 15 years are reported. Distribution of the haemorrhagic manifestations was in agreement with published data. On follow-up of the 40 splenectomized patients, the shortened platelet life-span, the reduced "recovery" as well as the increased rates of platelet turnover and platelet formation revealed a manifest tendency of normalization. One year after splenectomy the results were found "good" or "moderate" in 86%, more than two years after the intervention in 85%, of the cases. Retrospective analysis of the platelet-sequestration studies having shown "good" or satisfactory results in 93% of the splenic cases, this investigation is regarded as crucial to the indication of splenectomy. The absence of increased thrombocytopoiesis in approximately 15% of the cases is attributed to an antibody effect, reflected in a reduced polyploidy of the megakaryocytes. Normalization or increase in platelet count early after splenectomy is interpreted as a favourable prognostic sign. On the other hand, neither age of the patients nor the time of splenectomy was found to affect the success of the intervention. The results of corticosteroid treatment (Prednisolon 52%) lag far behind those of splenectomy. Ten patients were given combined immunosuppressive treatment.


Changes in protein, RNA and DNA content in various rat organs after long-term intake of ethanol. Male Wistar rats were given ethanol (approximately 25% of total caloric intake), while two different control groups were pair-fed isocaloric amounts of lipids or sucrose. After 7--10 weeks the following organs were studied: liver, cerebrum, heart, diaphragm, kidneys and testes. In fasted, ethanol treated rats there was a reduction in the hepatic concentration of RNA and the cerebral RNA/DNA ratio, when compared to both control groups, while no effects were found with respect to organ weight and amounts of protein, RNA or DNA in heart, diaphragm, kidneys and testes. When fed, ethanol treated animals were compared to both control groups, no effects on organ weight and composition were found in any tissue studied. Several significant differences were registered in the ethanol group as compared to one control group only, as well as between the two control groups. The consumption of ethanol (25% of total calories) thus caused only minor alterations in gross organ composition. These results also indicate the importance of interpreting with care any apparent effect of ethanol ingestion, unless at least two different control groups have been employed.


Studies on acute tolerance to ethanol in the abstinence period after long-term barbital treatment in the rat. Male rats were treated with sodium barbital in the drinking water for 18 weeks. The average weekly dosage was around 215 mg/kg in groups 1, 3 and 5. Groups 2, 4 and 6 were controls. Every week in the abstinence period after the barbital treatment the sensitivity to hexobarbital was tested with a threshold method after three different pretreatments. These pretreatments consisted of saline (groups 1 and 2) and ethanol (2.0 g/kg intraperitoneally) given either 0.25 hr (groups 3 and 4) or 2.5--3 hrs (group 5 and 6) prior to the hexobarbital test. Tolerance seen as a difference in the sensitivity to hexobarbital between groups 1 and 2 (saline pretreatment) were found on day 1, 8, 22 and 36 in the abstinence period. In groups 3 and 4 (tested 0.25 hr after ethanol) a tolerance was found on day 1 and 15. In groups 5 and 6 (tested 2.5--3 hrs after ethanol) a tolerance was only found on day 1. An acute tolerance to ethanol in the controls (seen as a difference between groups 4 and 6) was always recorded. Since tolerance in group 1 was not always accompanied by a tolerance in group 3, an acute tolerance to ethanol is unlikely as an unitary explanation to the tolerance induced by the barbital treatment, which instead seem to be part of much more complex changes. The acute tolerance to ethanol was influenced by the weekly administrations of ethanol used in the tests of the controls (groups 4 and 6) which means that acute tolerance could be one participant in these more complex changes.


Lithium effects on time estimation and mood in manic-melancholic patients. A study of diurnal variations. Behavioural measurements of time experience and phenomenological self-ratings of mood-variations (Beecher's Mood Scale) have been carried out at night and on the following morning in a group of lithium-treated patients, in a group of psychiatric patients not given lithium, and in an untreated group of healthy subjects. In all the groups investigated the internal "clock" was slower in the morning than in the night. The results indicated that the internal "clock" in lithium-treated patients was slower than in the two other groups, but only at night. Mood variations from night ot morning were observed in all three groups. The group of lithium-treated patients had fewer complaints as to self-report of mood-variations compared with the other groups.


Specific isolation of biologically-active peptides by means of immobilized anhydrotrypsin and anhydrochymotrypsin. Anhydrotrypsin, a derivative of bovine trypsin, immobilized on Sepharose tightly adsorbs various peptides containing L-arginine at the carboxyl termini, such as bradykinin and tuftsin. These peptides correspond to the specific products of the action of trypsin-like enzymes. Native trypsin immobilized on Sepharose does not show such strong affinity. Fragment 2, a peptide with 41 amino acid residues, which has been released together with bradykinin from bovine high-molecular-weight kininogen by the action of plasm kallikrein, is also adsorbed on the immobilized anhydrotrypsin. When only the carboxyl-terminal arginine is removed with carboxy-peptidase B, however, the peptide loses its adsorptive ability. Immobilized anhydrochymotrypsin, on the other hand, exerts specific affinity for the peptides which correspond to the products of chymotrypsin. These results suggest that the anhydro-derivatives of serine-proteseas in general may be of great use in the affinity chromatography of respective series of various naturally occurring peptides.


Determination of Hageman factor (HG, factor XII) and plasma prekallikrein (Fletcher factor) by radioimmunoassays. The titers of components of the plasma kallikrein-kinin system have been measured conventionally by their biological functions. The functional assays are, however, antagonized by the presence of inhibitors and/or the absence of potentiators in test samples. Immunologic assays obviate these difficulties. We have developed specific, sensitive and reproducible radioimmunoassays (RIA) for HF and prekallikrein, and have applied these assays to some clinical conditions. Normal pooled human plasma contained approximately 40 microgram of HF and 50 microgram of prekallikrein per ml. RIA were able to measure concentrations of HF and prekallikrein as low as 0.1% and 0.3% that of normal pooled plasma respectively. A good correlation existed between titers measured by clotting and radioimmunoassays among 40 normal subjects (correlation co-efficient = 0.82 for HF and 0.71 for prekallifrein). There was no significantly reduced in plasmas of patients with advanced liver cirrhosis or disseminated intravascular coagulation (DIC) and in cord serums, but they were normal in plasmas obtained after strenuous physical exercise and in plasmas of patients under treatment with warfarin.


A direct radioimmunoassay for human urinary kallikrein. A protein-binding radioimmunoassay (RIA) has been developed for human urinary kallikrein (HUK). HUK was purified to apparent homogeneity and rabbit anti-human urinary kallikrein serum was prepared. Radio-iodination of HUK was performed in 20 microgram batches with 1 mCi of 125I-Bolton-Hunter reagent in 0.1 M sodium borate buffer, pH 8.5, at 0 degree C. The 30 min reaction was terminated by adding 0.5 ml of 0.2 M glycine. Radiolabelled HUK was purified on a Sephacryl S-200 column (1x 50 cm) in 0.05 M Tris.HCl plus 0.2% gelatin, pH 7.4 (RIA buffer). 125I-HUK emerged as a single, uniform peak at Ve/Vo of 1.3. The RIA reaction mixture contained 15,000 cpm of 125I-HUK, 0.1 ml of diluted anti-kallikrein serum, 0.1 ml unlabelled kallikrein (1-100 ng) or the unknown sample and RIA buffer to a total of 0.5 ml. The reaction mixture was incubated at 22 degrees C for 18 hr, and 100 microliter to goat-anti-rabbit IgG serum was added to each tube. The tubes were incubated 18 hr at 4 degrees C, centrifuged 4,000 rpm for 30 min and, after decantation, the precipitate was counted for 125 I. The RIA reported here is sufficiently sensitive to detect 1 ng of kallikrein and should offer a useful technique to determine alterations of the kallikrein-kinin system in response to stimuli; both physiologic and pathologic.


Influence of vegetable protein on gallstone formation in hamsters. The lithogenic diet generally used for production of gallstones in hamsters contains 20% casein. In four separate experiments the 20% casein diet was compared with one containing 20% soy protein. All other components were kept constant. Two of the four experiments were of 45-day duration, one of 70 days and one of 100 days. When results of all four experiments were averaged, 57.5 +/- 3.6% of hamsters fed casein exhibited cholesterol gallstones whereas only 14.0 +/- 1.3% of soy protein-fed hamsters had gallstones. Thus, soy protein has a significant inhibitory effect on gallstone formation in hamsters. When soy protein was fed to hamsters with preestablished gallstones there was evidence of gallstone dissolution.


Ultrastructure of endometrial stromal foam cells. An endometrium with cystic-glandular hyperplasia contained large foam cells in the stroma. The majority had ultrastructural characteristics of endometrial stromal cells, although a few were interpreted as macrophages. Endometrial stromal cells that appeared normal by light microscopy contained varying quantities of lipid on ultrastructural examination, and differed from the predominate type of foam cell only by having less cytoplasmic volume and maintaining an elongated shape. Cells intermediate in size and shape between normal stromal cells and foam cells further substantiated the origin of most of the foam cells from endometrial stroma.


Estrogen receptor assay of mammary carcinomas. Effects of testosterone-estradiol-binding globulin (TeBG) and serum estradiol-17 beta. To test the hypothesis that the serum sex steroid-binding protein, TeBG, might contaminate mammary carcinoma cytosols sufficiently to interfere with assay for estrogen receptor (ER), studies of tritiated estradiol-17 beta (3H-E2) binding were done following saturation with steroid hormones or after heat treatment of cytosol. Cytosols with appreciable 3H-E2 binding consistently showed a high degree of saturability with nonradioactive E2 and diethylstilbestrol (DES), and much less saturability with 5 alpha-dihydrotestosterone (DHT). Furthermore, they manifested heat-lability of 3H-E2 binding. These characteristics indicated that little, if any, TeBG was being detected in most cytosols, and that the amounts of TeBG present were not sufficient to interfere with the ER assay. Study of the relationship between serum E2 concentration at time of removal of the carcinoma and results of ER assay confirmed the need to interpret negative ER assays obtained for premenopausal women cautiously when serum E2 levels exceed approximately 300 pg/ml.


Birth weight and gestational age in children with cerebral palsy or seizure disorders. Birth weight and gestational age of single-born children with cerebral palsy (CP) and those with seizure disorders were compared with norms for 40,000 single-born children in the same prospectively identified population. Low birth-weight and short gestation were important risk factors for CP, but these characteristics were uncommon, and the majority of children with CP were of normal birth weight and term gestational age. Preterm children with CP by age 7 years tended to have been even smaller at birth than was appropriate for their short gestions. Among term infants with later CP, the birth weights of the majority were appropriate for dates, but a subgroup were noticeably small for dates at term. Low birth weight, preterm birth, and smallness for dates at term were not significantly related to the risk of seizure disorders in children free of CP.


Bat-associated histoplasmosis in Maryland bridge workers. An epidemic of acute prolonged febrile respiratory disease affecting nine of 19 workers on a Maryland State bridge maintenance crew was diagnosed as histoplasmosis by serologic testing in all and by isolation of the organism in one. In our investigation, it was revealed that work on a particular bridge was associated with disease. Culture of bat guano from the site two months later revealed H. capsulatum. Four previously uninfected epidemiologic investigators also became ill with histoplasmosis following collection of soil and bat guano. This outbreak reveals that bats and bat guano are a source of histoplasmosis, suggests that only brief exposure is necessary for acute infection and reemphasizes that histoplasmosis is not confined to the midwestern states.


Campylobacter enteritis associated with unpasteurized milk. Campylobacter fetus ss. jejuni has recently been recognized as a human enteric pathogen. Laboratory isolation has been hindered by its fastidious nature. Methods for recovery of this organism from stool culture and a specific serologic test are described. An outbreak is reported in which three members of the same family became simultaneously ill with fever, severe abdominal cramps and diarrhea. C. fetus ss. jejuni was recovered from stool specimens from all three. A fourfold increase in serum immunoglobulin G (IgG) titer to this organism was demonstrated in each patient. All three patients had been consuming unpasteurized milk from a cow whose feces were infected with C. fetus ss. jejuni.


Rape: sexual disruption and recovery.

Rape: sexual disruption and recovery. In a longitudinal study of 81 adult rape victims reinterviewed four to six years later, effects of the rape on subsequent sexual functioning are analyzed. Most victims who had been sexually active were found to experience changes in frequency of sexual activity and in sexual response. Interview responses of victims are reported, and suggestions are offered for the counseling of rape victims and their sexual partners.


Plasma amino acid turnover rates and pools in rabbits: in vivo studies using stable isotopes. Gas chromatography--mass spectrometry of plasma amino acids has been used to determine the 15N enrichments of plasma glycine and alanine in rabbits in different metabolic states. Isotope-enrichment time-decay curves of plasma amino acids were linear over the course of the measurements after intravenous administration of a single dose of 15N-amino acid. Glycine and alanine pools and turnover rate constants were estimated from decay data. The effects of diurnal variation and fasting on glycine and alanine pool sizes, turnover rates, and flux in rabbits were studied to provide information on the effect of metabolic stress on amino acid kinetics in the whole body. The observations suggests that the transport of systemic glycine or alanine into the hepatocyte is under the control of a regulatory mechanism that compensates for decrease in the extracellular levels of the amino acids by enhancing the activity of the transport system. The volumes of the glycine and alanine pools were found to correspond to the extracellular space of rabbits, and the glycine and alanine pools can be identified as extracellular. We conclude that the plasma glycine and alanine 15N isotope-enrichment time-decay curves over the 1st h after a single intravenous dose of the amino acid represent mainly the hepatic uptake of glycine and alanine from the extracellular pool.


Functional state of adrenergic innervation of the stomach in rats with different stability of cardiovascular functions in experimental stress. Stress is induced in male Wistar and August rats by immobilising them for 30 hours. Nerve endings were studied using the method of fluorescent microscopy of Falck and Owman, modified by E. M. Krokhina. These studies showed that the dystrophic process related to stress acts on the activation system of the adrenergic innervation. This activation of transmitter synthesis in all the neurones is related to the large number of adrenergic transmitter substances found in the stomach wall. There are differences between animal species: August rats are more sensitive. This no doubt reflects a general instability in the vegetative functions of this species. The authors conclude that depending on the animal species there are factors in the stomach which may either afford resistance or predispose the organism to disorders of the cardiovascular system.


Pyrazidol, a new drug with antidepressant properties. During the search for new psychotropic drugs, a group of pyrazinoindole derivatives have been synthetized at the All Union Chemical Pharmaceutical Research Institute. Especially effective and having antidepressant activities is the hydrochloride of 1,10-trimethylene-8-methyl-1,2,3,4-tetrahydropyrazino (1,2-a) indole, named pyrazidol. Pyrazidol differs from any already known antidepressant for its chemical structure, the general pattern of activity and its neurochemical mechanism of action. The drug combines an inhibiting action on the neuronal uptake of monoamines with a monoamineoxidase inhibiting activity. As MAO-inhibitor, pyrazidol mainly impairs serotonin deamination, and acts only slightly on tyramine deamination. Furthermore, the anti-MAO action of pyrazidol is of short duration. Then, pyrazidol constitutes a drug with a particular profile of therapeutic activity.


Influence of social environment and of drugs on 3H-corticosterone uptake in various brain areas. Through specific cytoplasmic-nuclear receptors, brain appears as a target tissue for corticosteroids in their affecting neuroendocrine and behavioural activities. 3H-corticosterone (3H-B) uptake in various brain areas of differentially reared mice was studied in order to ascertain possible differences which might be connected to the different patterns of behavioural, neurochemical and stress responses. In 4-day adrenalectomized mice 1-h 3H-B uptake was higher in grouped than in isolated ones. Prlonged social stress in the grouped mice before adrenalectomy remarkably reduced 3H-B uptake. In 4-hour adrenalectomized dominant males, 4-h 3H-B uptake was higher than in submissive ones. All drugs tested (chlorpromazine, fluanisone, morphine, methergoline, naloxone, propranolol) affected 3H-B uptake. Knowledge of the interactions between behavioural manipulations or drugs and brain corticosteroid-receptors can improve the approach to the regulatory mechanisms of the hypothalamo-hypophyso-adrenal axis also in relation with behavioural phenomena.


Genetical studies of the palmar and sole patterns and some dermatoglyphic measurements in twins. The within- and between-pair mean squares and means have been estimated for dermatoglyphic patterns on finger-tips, palms and soles and compared between samples of 110 MZ and 111 DZ twins of Polish origin. Dermatoglyphic patterns have been represented by topologically significant pattern elements (loops and triradii) on finger-tips, palms and soles, considered separately and in various combinations, ridge counts on finger-tips and on palms and several other palmar and sole measurements. Some genetic parameters such as: genetic variance (GCT) based on within and between mean squares of the two types of twins, the within-pair variance ratio and the covariance/variance ratio in MZ twins have also been obtained for all these traits and considered in relation to differences in respect of the total and between-pair variances and means for all specified characters. The highest values of genetic parameters have been obtained for pattern intensities and ridge counts on finger-tips, considered separately or combined, for the H hypothenar loop and the axial t triradii on palms, and for the majority of sole loops and triradii. The lowest values have been found for several palmar loops and measurements such as minutiae counts. These results are, in respect of some pattern elements, not in agreement with the estimated heritability based on correlations between other relatives. A comparison of genetic parameters for single loops or triradii and for their various combinations indicates that some pattern elements or their combinations may be each influenced by a specific genetic system which modifies their phenotypic expression. It is believed that the obtained results are, for some proportion of characters, clearly biased by inequality of the total variances in MZ and DZ twins.


Airflow through the eustachian tube.

Airflow through the eustachian tube. In an attempt to distinguish normal from abnormal eustachian tube function, two groups of adults with nonintact tympanic membranes were tested. Six subjects had traumatic perforations of the tympanic membrane and a negative otologic histroy while five subjects had perforations as a sequela of otitis media. The subjects were tested with two methods: the middle ear inflation-deflation technique and a newly introduced forced-response technique. The comparison of the two groups revealed marked differences between normal subjects and patients with middle ear disease in active tubal dilation mechanisms and biomechanics of the eustachian tube. The forced-response test appeared to be a better method to determine the degree of actual tubal function.


A two-locus model for the inheritance of a familial disease. A model for the inheritance of a disease involving genes at just two linked loci is presented and discussed. One of the two pairs of opposite double homozygotes is assumed to lead to the disease and death. The other genotypes are assumed to be less fit than the double heterozygote. The cause of this reduced fitness may or may not be due to the disease. Conditions for the existence of a stable equilibrium are presented. The model has a sound biological basis and could be used to explain a wide range of disease frequencies and patterns of inheritance. Mutation is not required to explain why the disease persists in the population. Recurrence risks for sibs and twin concordance rates are derived and the consequences of the relaxation of selection against those with the disease are predicted. The effects of a selection model of the kind described on the amount of linkage disequilibrium in the population and on the estimation of the frequency of recombination are discussed.


Outbreak of botulism in Kenyan nomads.

Outbreak of botulism in Kenyan nomads. During disease surveillance in Kenya, a series of deaths were investigated among a group of nomadic Gabra in Marsabit. The cause was identified as botulism (Clostridium botulinum Type A), contracted from sour milk prepared traditionally in a gourd. Reported outbreaks of botulism in Africa would appear to be extremely rare.


The exsheathment of Brugia pahangi microfilariae under controlled conditions in vitro. Two reproducible techniques for the exsheathment in vitro of microfilariae of Brugia pahangi, and other sheathed microfilariae, are described. Microfilariae were isolated from infected cat blood by filtration and suspended in Hank's Balanced Salt Solution. The first technique involved the incubation of isolated microfilariae for one hour in 20 mM CaCl2 in a phosphate-free Balanced Salt Solution, during which time approximately 90% of the microfilariae lost their sheaths. The second method of exsheathing microfilariae of B. pahangi involved exposure of microfilariae to solutions of endopeptidase (5.8 units/ml) or papaya extract protease (3.0 units/ml) in Ca2+-free HBSS. Exsheathment rates of 95--100% occurred within 30 minutes in both enzyme solutions. Both the Ca2+ ion and the endopeptidase technique have proven equally effective in stimulating exsheathment of microfilariae of Brugia malayi, Wuchereria bancrofti and Litomosoides carinii. Such artificially exsheathed microfilariae are used for in vitro cultivation studies. The viability of Ca2+- and endopeptidase-exsheathed microfilariae of B. pahangi has been confirmed by inoculation of exsheathed larvae into susceptible female mosquitoes.


Twin growth: initial deficit, recovery, and trends in concordance from birth to nine years. Height and weight measurements for a large sample of twins from birth to nine years were used to construct growth curves for this period. Compared to singletons, twins were substantially smaller at birth, particularly for weight (30% deficit), but the latter showed a dramatic recovery in the first 3 months, then smaller increments until finally reaching the singleton norms at 8 years. Height, while less depressed at birth (17% deficit), was also slower to recover during the first year, then moved in comparable increments with weight until reaching parity with singletons. Prenatal influences on birth size were largely dissipated as each twin converged on his/her genetic growth curve. Monozygotic twins became progressively more concordant with age (R = 0.94 for height), while dizygotic twins became less concordant (R = 0.49). Ten monozygotic pairs with large birth-weight differences (greater than 750 g) were examined at 6 years; the smaller twin was still significantly lighter (P less than 0.01), marginally shorter (P less than 0.10), but not significantly lower in IQ. The results suggested a high degree of buffering for intelligence against the effects of nutritional deficit in the prenatal period. Some factors in addition to placental anastomosis are suggested as a possible basis for long-term size differences in monozygotic pairs.


Eye tracking and psychopathology. New procedures applied to a sample of normal monozygotic twins. New methods for examining eye movements were developed and applied in a study of young, adult monozygotic twins. Subjects, tested twice, engaged in smooth pursuit tracking at different target frequencies, followed a stimulus requiring saccadic eye movements, performed a related psychomotor hand tracking task, and tracked a target while monitoring changes in the stimulus display. Analysis of test-retest reliability and twin concordance suggested that performance on these tasks characterized stable traits and were consistent with other reports implicating a genetic contribution to tracking ability. Special consideration was given to the probable role of attention in producing various types of tracking deficit. Estimates of the incidence of tracking dysfunction and correlations with psychometrically measured personality traits were examined.


[X-ray anatomic features of the skeletons of twin children]. The size of right and left middle phalanges in the II-V fingers and the III finger have been studied in 108 pairs of monozygotic and dizygotic twins at 8--19 years of age and in 60 paris (pedagogical experiment) of separated twins (from the same pair), schoolchildren of the 2d--5th forms trained according different programs of physical culture. A great similarity of osteometric signs has been stated in monozygotic twins. As to local (intradigital) differences, a prevalence of the IIId finger should be mentioned. Maximum of genetic determination is evident for transversal growth--under high mechanical loadings on the bones, for longitudinal--under low mechanical loadings. The data of the pedagogical experiment demonstrate that increased mechanical loading on the hand bones activates osteogenesis. According to the majority of indices the main is the "radial" (II--III fingers) type.


[New modification of the technic for preserving human brain preparations]. The modification suggested is a combination of two methods--one with formalin application, another--without formalin application. At first, 5% solution of formalin is injected into the brain arterial bed, then it is injected with an artificial neoprene resine--latex. The preparation is put into a preserving liquid containing no formalin (a mixture of glycerin--45%, acetous potassium--10%, water--45%) for 1.5--2 months.


[Morphology of the lymphoid system in the perinatal period under conditions of antigenic stimulation]. Lymphoid tissue of 29 fetuses and newborns (13 controls and 16 with infections) was studied. In premature babies the thymus responds to antigenic stimulation by accidental involution of the immature type. In addition to the latter, under conditions of the antigenic stimulation the thymus shows either premature maturation with mature reaction, or hypoplasia, or no response (inert thymus). In most cases the antigenic stimulation speeds up maturation of the peripheral lymphoid tissue as confirmed by morphometrical data. Depending on the antigen, however, hypoplasia of the thymus and of the peripheral lymphoid tissue may be observed. Localized infection develops with mature immune system, generalized in immature immune response.


Plasma thyroid hormone and glucocorticosteroid concentrations in the male rat following prolonged exposure to stress. Exposure of male CSF rats to a signalled unpredictable 60-day stress regimen induced a significant elevation in circulating triiodothyronine (T3) concentration above the control for the first 20 days of stress before the rate of secretion returned to normal. On the other hand, circulating thyroxine (T4) concentration fell significantly below the control value for the first 5 days of stress before the normal rate of secretion was reached in 10 days. A histological study of the thyroid gland revealed no change in activity among any of the control and stressed groups. At the same time this regimen also induced an initial extreme corticosterone elevation which was maintained for the first 5 days of stress and thereafter gradually fell to re-establish a new level by 40 days with no further change up to 60 days of stress. The possible physiological significance of the marked elevation in T3/T4 ratio as a result of stress is discussed, in particular with relation to higher glucocorticoid secretion.


Interaction of Y-chromosomal and autosomal gene(s) in the development of intermale aggression in mice. It has been suggested that the Y chromosome of DBA/1Bg mice makes an incremental contribution to their aggressive behavior and to that of the C57BL/10 female X DBA/1 male F1 hybrids. To test this hypothesis, a congenic stock of C57BL/10 with the DBA/1 Y chromosome was developed by the backcross system of breeding; the stock is designated C57BL/10-Y1. There were no significant differences in aggressive behavior between the congenic C57BL/10 and C57BL/10-Y1. However, the hybrid B10D1 F1 and D1B10-Y1 F1 had identical aggression scores, and both of these were more aggressive than the hybrid D1B10 F1. These findings support the hypothesis that there is an interaction between DBA/1 Y chromosomes and autosomes in the development of intermale aggression of these mice.


Medium-chain fatty acid synthesis in lactating-rabbit mammary gland. Intracellular concentration and specificity of medium-chain acyl thioester hydrolase. The concentration of medium-chain acyl thioester hydrolase and of fatty acid synthetase was determined by rocket immunoelectrophoresis in nine different particle-free supernatant fractions from lactating-rabbit mammary gland. The molar ratio of the hydrolase to fatty acid synthetase was 1.99 +/- 0.66 (mean +/- S.D.). A rate-limiting concentration of malonyl-CoA was required to ensure the predominant synthesis of medium-chain fatty acids when 2 mol of the hydrolase was added per mol of fatty acid synthetase. The interaction of the hydrolase with fatty acid synthetase was concentration-dependent, though an optimum concentration of hydrolase to synthetase could not be obtained. The lactating-rabbit mammary gland hydrolase altered the pattern of fatty acids synthesized by fatty acid synthetases prepared from cow, goat, sheep and rabbit lactating mammary glands, rabbit liver and cow adipose tissue.


The polypeptides of isolated brain 10nm filaments and their association with polymerized tubulin. Brain 10 nm filaments were isolated from bovine, rabbit and rat brains by a modification of an existing procedure. The overall polypeptide composition of these preparations was similar to that previously reported for brain neurofilaments. In addition to the major polypeptide component, which has mol. wt. approx. 50 000, three other polypeptides with chain mol. wts. approx. 210 000, 155 000 and 70 000, which correspond to peripheral-nerve neurofilament polypeptides, were consistently found to be present. The mol. wt.-50 000 species was found to be heterogeneous and may contain a component derived from the mol. wt. 70 000 polypeptide. The three higher-molecular-weight polypeptides did not appear to be obviously homologous or to be homologous with myosin or Myxicola neurofilament polypeptides. These same three higher-molecular-weight components were shown to be identical with the polypeptides probably responsible for the 10 nm filaments formed during the early cycles of the tubulin-purification protocol.


[Changes in plasma dopamine-beta-hydroxylase activity in patients with acute subarachnoid hemorrhage (author's transl)]. In 24 patients with subarachnoid hemorrhage (SAH) who were admitted within 48 hours after the onset, the activity of dopamine-beta-hydroxylase (DBH) in peripheral venous plasma was analyzed applying the method described by Nagatsu and Udenfriend (Clin. Chem., 18: 980-983, 1972) with a minor modification. Plasma samples were serially collected every a few days for three days to four weeks after the onset. DBH activity in peripheral venous plasma increased markedly after the onset, reaching the highest level within 48 hours, and thereafter declined time-dependently for about two weeks. There was no significant difference in the plasma DBH activities on admission between patients with and without cerebrovascular spasm revealed by angiography. The decline of the activity was significantly remarkable in patients with spasm compared with those without spasm. The difference was most prominent around the 7th day after the onset when spasm was shown most frequently. Neurosurgery or administration of analgesics and/or sedatives had little effect on the changes in plasma DBH activity in acute SAH. The activity correlated with the pressure of cerebrospinal fluid (r = 0.587, P less than 0.05), when it was higher than the normal range. With these results we obtained following: 1) The activity of sympathetic nervous system increases following SAH for a week after the onset. 2) The activity declines more rapidly in patients with cerebrovascular spasm than those without spasm, when it was judged from the activity of plasma DBH activity.


A radioimmunoassay for cytosine arabinoside. A radioimmunoassay (RIA) for cytosine arabinoside (AraC) has been developed using antiserum raised in a sheep to an AraC monophosphate-ovalbumin conjugate. The antibody shows only 0.008% cross-reactivity with uracil arabinoside (AraU) and low (0.023%) cross-reactivity with other commonly co-administered drugs such as cytotoxic and antibacterial agents, and also a number of naturally occurring nucleosides and nucleotides. It does however cross-react by 125% with AraC monophosphate and by 109% with AraC triphosphate. As little as 1 ng/ml of AraC can be detected in plasma, serum, urine and cerebrospinal fluid (CSF) with no need for prior extraction. This RIA has been used to follow the disappearance of AraC from the plasma of patients receiving the drug.


Characterization of the genome of the basidiomycete Schizophyllum commune. DNA of Schizophyllum commune was isolated both from mycelial cells and from protoplasts. Nuclear DNA was isolated after solubilization of the mitochondria with the detergent Nonidet. The G + C content of the nuclear DNA was 57%, calculated from its buoyant density (1.7165 g/ml) and from the Tm (77.4 degrees C in 15 mM NaCl/1.5 mM trisodium citrate). The buoyant density of the ribosomal cistrons was 1.707 g/ml. DNA isolated from purified mitochondria had a very low G + C content: 22% (rho = 1.6845 g/ml, Tm = 61.8 degrees C in 15 mM NaCl/1.5 mM trisodium citrate). Analysis of CsCl profiles and melting patterns suggested that mitochondrial DNA contains interspersed (A + T)-rich sequences. From reassociation analysis of sheared nuclear DNA the genome size of S. commune was determined to be 22.8 . 10(9) daltons. A small amount of DNA (0.5 . 10(9) daltons) bound to hydroxyapatite at zero time Cot. 7% of the genome (1.6 . 10(9) daltons) represented repetitive DNA.


Relative hydrophobicity of surfaces of erythrocytes from different species as measured by partition in aqueous two-polymer phase systems. Erythrocytes from different species were subjected to partition in an aqueous, buffered Ficoll/Dextran two-phase system. The effects of different salt composition of the phase system on the distribution of erythrocytes was examined. Different ratios of sodium chloride to sodium phosphate buffer (pH 7.4) with the ionic strength varying from 0.176 to 0.288 M were used in the systems and similar relationship between the partition coefficients of the cells under study and the ionic strength were established. The relationships were treated according to a general equation previously established (Zaslavsky, B.Y., Miheeva, L.M., Metechkina, N.M., Pogorelov, V.M. and Rogozhin, S.V. (1978) FEBS Lett. 94, 77-80) and the results obtained were used to evaluate the relative hydrophobicity of the cells' surface.


[Isolation and properties of lactate dehydrogenase isoenzymes from loach (Misgurnus fossilis) skeletal muscles and eggs]. The main lactate dehydrogenase (EC 1.1.1.27) isozyme from loach (Misgurnus fossilis) skeletal muscles was purified to homogeneity by polyacrylamide gel electrophoresis. The main group of lactate dehydrogenase isozymes which predominate in their activity in the unfertilized eggs of this teleost species and are stable to AgNO3 inhibition were partially purified. The effects of various concentrations of pyruvate, oxalate and urea on the activities of these purified enzyme preparations and their pH optima were studied. The antiserum for the purified lactate dehydrogenase isozyme from loach skeletal muscle was obtained. The decrease of the activity of this isozyme and that of the investigated group of isozymes from the eggs in the presence of increasing concentrations of antiserum was estimated.


Analysis of dichotomous response data from certain toxicological experiments. In certain toxicological experiments with laboratory animals, littermate data are frequently encountered. It is generally recognized that one characteristic of this type of data is the "litter effect", i.e., the tendency for animals from the same litter to respond more alike than animals from different litters. In this paper attention is restricted to dichotomous response variables that frequently arise in toxicological studies, such as the occurrence of fetal death or a particular malformation. Various techniques for estimating the underlying probability of response are discussed. A number of generalized models that have recently been proposed to take the litter effect into account are breifly reviewed and compared to the simpler binomial and Poisson models. Various procedures for assessing the significance of treatment-control differences are presented and their relative merits discussed. Finally, future research needs in this area are outlined.


[Activation of lipid peroxidation in emotional-pain stress]. Accumulation of primary and secondary products of lipid peroxidation (PLP) in different tissues of Wistar rats under emotional-pain stress (EPS) was studied using UV-spectrophotometry and fluorescense of Schiff bases. It was shown that under EPS the amount of PLP increased mostly in the heart and to a lesser degree in the skeletal muscle and brain. An increase in hydroperoxidases in all the organs studied was less than that in the PLP end-products, i. e. flourescent Schiff bases.


[Analysis of the effect of morphine on the reproductive capacity and immunological status of mice]. Embryogenesis process is disturbed under the action of prolonged morphine administration to CBA mice. Simultaneously a decrease in the level of antibody-synthesizing cells and a significant reduction in the cooperating interaction of T and B lymphocytes in response to the injection of sheep red blood cells are noted. At the same time stimulation of bone marrow cells and specific sensitization of MIF-inducers to the antigen from the brain of morphinized mice are revealed.


[Sex ratio in hybrid mice CBA X C57BL].

[Sex ratio in hybrid mice CBA X C57BL]. Sex ratio and postimplantation mortality were studied in (CBAXC57BL)F1, CBA and C57BL mouse embryos. It has been shown that female fetuses are predominant in the progeny of hybrid mice. In CBA and C57BL mice the sex distribution was 1 : 1. The disorder in the balanced sex ratio in the progeny of hybrid mice confirms a conclusion on the effect of the mouse genetic features on the sex distribution in embryos. Equal sex ratio in CBA and C57BL mice indicates the absence of selective mortality in the embryos of either sex during embryogenesis.


[Mitotic activity of the lymphocytes of the thymus cortex in hypokinesia during the period of readaptation]. The changes in the weight and mitotic index were studied in the cortex of the thymus of Wistar rats during 10-day hypokinesia and 10-day readaptation (restoration). 24 hours after immobilization of the animals the mitotic index was 2 times as lower. No complete readaptation was attained during 10-day hypokinesia. No readaptation was attained during 10-day hypokinesia. In readaptation the stage of secondary stress was found (the mitotic index was 3.5 times as reduced), the stage of genuine restoration being revealed after 10 days.


[Active avoidance without discriminating control as a model for the study of protective effect of drugs in emotional stress]. The method of plotting of hystograms of distribution according to the frequency intervals between pressing the redal (the method of active avoidance with no discriminating control) permits one to estimate slight shifts in the character of operative activity of rats occurring under the effect of emotional stress. The design of the simple multichannel apparatus for developing and studying of habits of active avoidance in several animals is presented.


AET-treated platelets: their usefulness for platelet antibody detection and an examination of their altered sensitivity to immune lysis. 2-Aminoethylisothiouronium bromide (AET) increases the sensitivity of blood cells to complement-mediated immune lysis. We compared the sensitivities of untreated or AET-treated platelets to immune lysis induced by different types of platelet antibody in the 51Cr platelet lysis test. AET platelets were 8-16 times more sensitive to autoantibody and alloantibody, but 8-16 times less sensitive to drug-dependent antibody. AET-platelets bound similar amounts of alloantibody but less drug-dependent antibody, and they lysed at higher complement dilutions than did untreated platelets. AET-platelets detected 10 of 25 autoantibodies, 9 of 9 alloantibodies, and 5 of 8 drug-dependent antibodies. Untreated platelets detected 1 of 25, 6 of 9, and 7 of 8 of these respective platelet antibodies. The use of AET-platelets in the 51Cr platelet lysis test increases its sensitivity for detecting non-drug-dependent platelet antibodies. AET-platelets resemble paroxysmal nocturnal hemoglobinuria (PNH) platelets in their enhanced sensitivity to complement-mediated lysis. They differ from PNH platelets in their insensitivity to immune lysis induced by drug-dependent antibodies and, in this respect, are similar to Bernard-Soulier syndrome platelets.


Effects of the oestrous cycle and exogenous ovarian steroids on metabolism of beta-phenylethylamine in rat lung. 1 Metabolism of [14C]-beta-phenylethylamine (PEN), a substrate for monoamine oxidase-B (MAO-B), was measured in lung homogenates and in perfused lungs during the 4 day oestrous cycle of the rat. 2 Metabolism in vitro was high during met-oestrus and di-oestrus and low during pro-oestrus and oestrus; this variation in activity correlated with changes in Vmax of the enzyme without changes in Km. 3 PEN metabolism in lung homogenates was also altered by treatment of rats with 17 beta-oestradiol but not by progesterone treatment. 4 Metabolism of [14C]-PEN in perfused lungs was the same during either pro-oestrus or met-oestrus. Uptake of [14C]-PEN in perfused lung measured directly was also the same at these two stages. 5 These results demonstrate that in lungs MAO-B activity was affected by endogenous changes in steroid level but that such changes in enzymic activity were not reflected in the metabolic properties of whole lung.


Production of catalepsy and depletion of brain monoamines by a butyrophenone derivative. 1 The cataleptic and monoamine-depleting effects of a butyrophenone derivative (4'-fluoro-4-[[4-(p-fluorophenyl)-3-cyclohexen-1-yl]-amino]-butyrophenone hydrochloride, U-32, 802A) were studied in rats and mice and compared with those of tetrabenazine. 2 Catalepsy was evaluated by means of a modified grid test which allowed the repetition of the test in the same animal several times without affecting the results. Both drugs produced a dose-related cataleptic state of similar time course. 3 Like tetrabenazine, U-32, 802A induced a large reduction in the content of 5-hydroxytryptamine, dopamine and noradrenaline in different parts of the brain, with a concomitant elevation in the metabolites 5-hydroxyindol-3-yl acetic acid and homovanillic acid. The time courses of the catalepsy and the reduction in brain monoamines were very similar. 4 The activity of U-32, 802A suggested that the drug, although chemically a butyrophenone, might act primarily at the presynaptic organelle for storage of monoamines in a way similar to tetrabenazine.


The oral activity of delta'-tetrahydrocannabinol and its dependence on prostaglandin E2. 1 delta'-trans-Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06 mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man. 2 Comparison with chlorpromazine in mice shows that chlorpromazine and THC are equipotent as cataleptics during the first 2 h after dosing; thereafter the THC activity increases to a peak when it is 5.67 times as active as chlorpromazine. 3 The cataleptic effect of THC is abolished by aspirin, indomethacine, diffunisal and phenylbutazone which inhibit the biosynthesis of prostaglandins and is restored by exogenous prostaglandin E2 (PGE2) but not PGE1 and PGF2 alpha. This suggests that the effect of THC depends upon the presence of PGE2. 4 In contrast, the cataleptic effect of chlorpromazine is not affected by pretreatment with aspirin. 5 THC is very much less active intraperitoneally than orally; our results suggest this is not due to poor absorption or extraction into fat depots. 6 Cannabidiol has no cataleptic effect.


Duct ectasia in the male.

Duct ectasia in the male. Three cases of inflammatory duct ectasia occurring in the male breast are described. The clinical presentation of the disease in the male closely resembles that in the female. Nipple retraction, nipple discharge, periareolar inflammation and bilateral involvement are all seen. Conservation measures produced unsatisfactory results similar to those in women. A similar operative approach to that used in women is advocated.


Morphine withdrawal syndrome: differential participation of structures located within the amygdaloid complex and striatum of the rat. The participation of amygdaloid and striatal structures in the various signs of morphine withdrawal syndrome (MWS) has been investigated using two complementary approaches: intracerebral application of naloxone in various nuclei of dependent rats and effects of various lesions and transections on systemically induced MWS. In morphine dependent rats local application of naloxone (10 micrograms in 0.1 microliter solution) in the vicinity of either the central nucleus of the amygdala or the lateral anterior nucleus but not in adjacent amygdaloid or striatal nuclei elicited the jump sign. Diarrhea was more frequently elicited by application of naloxone in the striatum or centromedial amygdala than the basolateral parts of the complex. In contrast, there was no specific anatomical correlates to the remaining signs including wet shakes, paw tremor, teeth chattering and chewing. Bilateral electrolytic lesion of the central amygdala or combined transection of the stria terminalis and so-called ventral amygdalofugal pathway eliminated the jump without affecting the remaining signs. In contrast a large bilateral destruction of the entire striatrum did not significantly affect the various signs. Bilateral transection of the stria terminalis reduced only the occurrence of the wet shakes. Also, a transection of the medial forebrain bundle considerably reduced the 3 main signs, i.e. jump, wet shakes and diarrhea. These results suggest that, in analogy to the acute actions of morphine, MWS should not be considered as a unitary phenomenon but as an ensemble of signs which probably reflect the intense activation induced by naloxone in a number of brain sites consequent to the abrupt interruption of opioid actions in a dependent animal. The significance of these results is discussed with reference to previous anatomical, biochemical and behavioural studies performed on the amygdala.


Filamentous contacts containing subjunctional dense lattice and tubular smooth endoplasmic reticulum in cat lateral geniculate nuclei. Ultrastructure of filamentous contacts was examined in the cat lateral geniculate nucleus. This intercellular contact was classified into two types, asymmetrical and symmetrical, according to its fine structure. (1) The asymmetrical filamentous contact had a different fine structure on the cytoplasmic sides of its apposed membranes. This sort of contact occurred between the postsynaptic components of principal cells and the presynaptic terminals of either optic nerve or interneurons. The membrane on the presynaptic side showed a wavy outline. Plaques of cytoplasmic density were located on the crests of the wave. On the postsynaptic side cytoplasmic dense material formed a regularly arranged latticework on the membrane, 'subjunctional dense lattice'. The dense lattice was closely associated with underlying smooth surfaced endoplasmic reticulum and mitochondria, so as to form a subjunctional complex consisting of these 3 organelles. Two filamentous structures, neurofilaments and microtubules, enter and leave this subjunctional complex. (2) The symmetrical filamentous contact occurred between two principal cell components. Nearly the same fine structural arrangement as that on the postsynaptic side of the asymmetrical contact was present in the cytoplasm on the both sides of this junction.


Somatosensory inattention after dopamine-depleting intracerebral 6-OHDA injections: spontaneous recovery and pharmacological control. The unilateral injection of 6-hydroxydopamine into the area ventralis tegmenti of rats pretreated with desmethylimipramine resulted in an inattention to somatosensory stimuli impinging on the contralateral body surface. Three separate groups of rats could be identified, that varied in their behavioral deficit: (1) 7 rats showed no recovery of orientation to touch during 4 months postoperatively; (2) 8 showed a marked loss of orientation followed by recovery that was nearly complete within one month; (3) 11 showed a minimal deficit in orientation. Those rats that did recover showed a characteristic pattern: orientation began first to touch of rostral body points (e.g. snout) and only later to touch of caudal body regions. The administration of low doses of alpha-methyl-p-tyrosine or spiroperidol to rats that had spontaneously recovered from their somatosensory loss reinstated their contralateral inattention while not affecting their orientation to ipsilateral touch. As these drugs took effect, orientation was affected first at the caudal body points and only later at more rostral regions. As the drug effects dissipated, orientation was restored rostrocaudally. High correlations were observed between neostriatal DA and the extent of somatosensory orientation observed immediately after surgery (r = +0.76) or during the entire postoperative month (r = +0.66). While the results point clearly to the role of neostriatal DA loss in the somatosensory inattention syndrome, a loss of the DA-containing terminals in olfactory tubercles and nucleus accumbens septi may contribute to this impairment.


The sensitivity of some avian viruses to formaldehyde fumigation. Various avian viruses (infectious bursal agent, reovirus, adenovirus, infectious bronchitis, Newcastle disease, poxvirus, avian encephalomyelitis and infectious laryngotracheitis virus) as suspensions in buffer or in a litter slurry were exposed to aerosolized formalin in an attempt to determine the efficacy of this fumigation method for decontamination of laboratory isolation cubicles. Formalin (37% formaldehyde) was delivered by a commercial insecticide fogger at a flow rate of 40 ml per minute and a volume of 36 ml per cubic meter of space. Fumigated cubicles were left sealed for 18 hr (cycle 1) before viruses were sampled, or were then exposed to a second fumigation and left sealed for an additional six hour period (cycle 2) before viruses were titrated (commencing at a 1:10 dilution) for residual infectivity. Although the infectivity of all viruses was reduced by over 99% by one fumigation cycle, the second cycle was necessary for reduction of Newcastle disease and reoviruses to non-detectable (no infectivity demonstrated in a 1:10 dilution of fumigated virus) levels.


Management of disseminated testicular cancer. Thirteen patients with disseminated nonseminomatous germ cell tumours of the testis were treated with a three-drug combination (vinblastine, bleomycin and cis-diamminedichloroplatinum). Of 12 patients with measurable disease, 8 had complete and 3 partial remission. One patient with a solitary metastasis failed to respond but is disease free following surgical excision. Toxicity was moderate but no drug-related deaths occurred and there were no apparent lasting side-effects. No patients with complete remission have relapsed. Ten of the 13 patients are without evidence of disease from 9 to 36 months after treatment, 6 of these for 2 years or more. One patient died after a partial remission of 16 months. One is undergoing further treatment for relapse with liver metastases and one remains in partial remission at 30 months. These results demonstrate the efficacy of this drug combination in testicular cancer.


Early detection of micrometastases via flow microfluorimetry. We show that by measuring the joint distribution of fluorescent and scattered light in a suspension of lung taken from the C57B1/6J mouse, we are able to discriminate in vivo between the lung metastases of the B16 melanoma and the normal lung tissue. We can in such a way detect metastatic cells in a very early stage of growth and also obtain growth curves for the metastatic population. We analyze the sensitivity of the method of detection and speculate how it might be used in aiding in human diagnosis.


Tumor promoters induce changes in the chick embryo fibroblast cytoskeleton. We have examined the effect of the tumor promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), on the actin-containing elements of the cytoskeleton of chick embryo fibroblasts (CEF). TPA at concentrations as low as 7.3 times 10-10M indices a reversible change in the cytoskeleton as visualized by indirect immunofluorescence using anti-actin antibodies. Cells incubated with TPA lose the ordered actin-containing structures found in normal cells and resemble Rous sarcoma virus-transformed cells in that the immunofluorescent actin pattern is diffuse. The TPA effects are both dose-and time-dependent. Analogs of TPA which are inactive as tumor promoters do not induce cytoskeletal changes at the concentrations tested, while a second tumor promoter, PDD, is also able to cause alterations in actin-containing structures. The action of TPA requires de novo synthesis of both RNA and protein. The direct cytoskeletal changes are neither plasmin-dependent nor subject to inhibition by incubating the cells with high levels of protease inhibitors during the exposure to TPA. However, plasminogen does increase the sensitivity of cells to TPA.


The concomitant effect of unsaturated fatty acid supplemented to medium on cellular growth and membrane fluidity of cultured cells. The membrane fluidity of cultured Yoshida sarcoma cells was determined under the culture condition in which various amounts of saturated and unsaturated fatty acids were supplemented to a serum-free medium containing defatted bovine serum albumin. The greater amount of unsaturated fatty acids was supplemented to the medium, the more active membrane fluidity and cellular growth were enhanced, while the supplementation of a saturated fatty acid had no such effect.


Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects. The hemodynamic effects of intravenous verapamil administration were examined in 27 patients with hypertrophic cardiomyopathy. Increasing doses of verapamil produced small increases in heart rate and cardiac output and a significant decrease in systolic blood pressure, but had no significance effect on mean pulmonary artery wedge pressure or left ventricular end-diastolic pressure. The highest dose of verapamil increased heart rate from 72 +/- 3 to 81 +/- 6 beats/min and reduced systolic blood pressure from 118 +/- 8 to 99 +/- 5 mm Hg (p less than 0.005). This dose decreased the basal left ventricular outflow tract gradient from 94 +/- 14 to 49 +/- 14 mm Hg and the average left ventricular outflow tract gradient during the Valsalva maneuver from 76 +/- 5 to 63 +/- 13 mm Hg, during amyl nitrite inhalation from 69 +/- 15 to 39 +/- 13 mm Hg, and during isoproterenol infusion from 108 +/- 29 to 70 +/- 21 mm Hg (p less than 0.01). These results indicate that verapamil can significantly decrease left ventricular outflow obstruction in patients with hypertrophic cardiomyopathy and thus may provide an important new therapeutic agent in the treatment of this disorder.


Acute triclofos poisoning in a preterm infant. A preterm infant with accidental triclofos sodium poisoning is described. He developed deep coma, severe hypothermia, mild by hypotension and lack of the primitive and deep tendon reflexes. During recovery, the primitive reflexes were the last to appear. The natural course of triclofos poisoning, and its influence on the immature central nervous system of the preterm infant are discussed.


Review: children and companion animals.

Review: children and companion animals. The literature concerning the relationship between the child and companion animal is reviewed including the possible use of companion animals as aids in the psychotherapy of children. The literature pertaining to cruelty to animals is also discussed. It is concluded that the evidence available is sufficient to justify further research into interactions between children and companion animals both in therapy and in the population generally, and some possible approaches are suggested.


[Morphological and ultrastructural changes in the liver of rats on a low-protein diet regimen and in alcoholic intoxication]. The present study aims to clarify some discussion problems on the role of protein deficit in the diet during alcohol action. They carried out studies on rats, part of which received alcohol with whole protein diet, but other part -- low protein diet. The results from the morphological examination showed that lack of proteins in food was of substantial significance and increased pathological changes in liver, due to alcohol effect.


[Pure gonadal dysgenesis. Case report with unusual anatomical and endocrine findings]. The syndrome of pure gonadal dysgenesis (PGD) cannot always easily be distinguished from other disorders of gonadal development. Relations are evident with Turner's syndrome, females with hypoplastic ovaries, male pseudohermaphroditism, mixed gonadal dysgenesis and the vanishing testes syndrome. The case is reported of a 40 year old female with primary amenorrhea, alopecia, eunuchoid features, XY karyotype with normal breast development and sexual hair after estrogen therapy. On laparotomy streak ovaries were found at ovarian site. Pathohistological examination revealed on the left side wolffian duct remnants such as ductuli deferentes and epididymis besides sparse Leydig-(hilus-)cells and on the right side only a rudimentary fallopian tube with subendothelial accumulation of hyperplastic Leydig-(hilus-)cells. Serum-testosterone elevation above the normal female range (630 ng/dl) persisted following gonadectomy (151 ng/dl). Ectopic Leydig-(hilus-)cells were regarded responsible for the continuing testosterone production. The present case lies on borderline between PGD and mixed gonadal dysgenesis because remnants of wolffian duct derivatives suggest unilateral fetal testicular activity; classification as PGD however was justified in purely female body features and lacking evidence of testicular tissue.


Some aspects on the organization of microfilaments and microtubules in relation to nondisjunction. One possible mechanism behind nondisjunction is a malfunctioning spindle. A defect or lack of spindle is a criterion for c-mitosis. In chemical mutagenesis research the c-mitotic effect is a well known cytological phenomemon, which can be induced by many different compounds. Pioneer work was performed during the 1940's by Ostergren and Levan, and their results and conclusions are briefly discussed. Since colchicine can induce c-mitosis and c-meiosis, by definition, and nondisjunction, a correlation between these phenomena is logical. The general importance of the spindle protein tubulin is considered and some new data from the cell biology literature on spindle formation and function as well as chromosome structure are briefly summarized. This knowledge can be used to correlate cytological and biochemical parameters among which c-mitosis and changes in sulfhydryl group metabolism after chemical treatment are the most obvious ones.


Interaction between prealbumin and retinol-binding protein studied by affinity chromatography, gel filtration and two-phase partition. The interaction between prealbumin and apo or holo retinol-binding proteins has been studied by affinity chromatography, gel filtration and two-phase partition. At physiological ionic strength apo and holo retinol-binding protein form 1:1 molar complexes with prealbumin. Mean dissociation constants for the prealbumin compex with apo retinol-binding protein and holo retinol-binding protein with all-trans retinol, retinoic acid, retinal and retinyl acetate were calculated from the partition data as 0.33 +/- 0.11 x 10(-6) M and 0.075 +/- 0.015 x 10(-6) M respectively (mean +/- S.E.M.). The difference was statistically significant. Quantitative data on the amount of retinol, retinol-binding protein and prealbumin in plasma and urine were in good agreement with the ratio of the dissociation constants for the complexes of apo and holo retinol-binding proteins with prealbumin as determined in the partition experiment. The magnitude of the dissociation constants was compatible with previously published data on the turnover of retinol-binding protein.


Impaired gastric function in children with cow's milk intolerance. Eight infants with cow's milk intolerance (CMI) were studied for basal and maximal gastric acid secretion and the fasting serum gastrin level. All these patients had clinical malabsorption. Jejunal biopsies revealed subtotal villous atrophy in six children and slight changes in the remaining two. The mean maximal acid secretion in the infants with CMI was significantly decreased being 85 +/- 78 mumol/h/kg (mean +/- SD), as compared with a control group of the same age with a corresponding value of 233 +/- 66 mumol/h/kg. The fasting serum gastrin level was elevated, being 104 +/- 116 pmol/l in the study group and 37 +/- 10 in the controls. Three infants with CMI underwent gastric biopsy. Marked changes with epithelial degeneration and prominent cellularity in the lamina propria were seen in two patients. The injury was most severe in the antrum of the stomach. When these patients with CMI were treated with human or soy milk, the maximal acid secretion returned normal in six months.


Asplenia syndrome in one of mono-zygotic twins. One of mono-zygotic twins who had the asplenia syndrome with severe cardiac malformations is described, the other twin being normal. This is the first documented case of situs ambiguus in mono-zygotic twins. The relationship of situs ambiguus to situs inversus, which has previously been described in a number of mono-zygotic twin pairs (some concordant and some discordant) is unclear.


High levels of transition metals in dinoflagellate chromosomes. X-ray microanalysis of fixed, sectioned chromosomes of the dinoflagellates Glenodinium foliaceum, Prorocentrum micans and Amphidinium carterae has revealed high levels of iron, nickel, copper and zinc. We report high levels of these transition metals in association with chromosomes in intact eukaryote cells.


Genetic dissection of the Drosophila circadian system. Genetic experiments involving selected strains as well as single gene mutations have provided information concerning the organization of the Drosophila circadian system. The phase of the emergence rhythm of D. pseudoobscura can be altered by genetic selection without significantly affecting the phase and period of the light-sensitive pacemaker. The period of the D. melanogaster pacemaker, over the range 19 hours to 29 hours, can be encoded in the DNA sequence of a single genetic locus. The short-period and long-period mutations do not eliminate the pacemaker's temperature compensation mechanism. The short-period mutation alters the resetting behavior of the pacemaker from weak (type 1) in wild-type to strong (type 0) in the mutant. Five aperiodic mutations isolated in D. pseudoobscura belong to two complementation groups. In complements bearing one mutation from each group, the periodicity of the pacemaker is wild-type, but the phase of the emergence rhythm is 5 hours later than wild-type. Thus mutations in particular genetic loci have dramatic effects on the basic properties of circadian pacemakers and rhythms.


Metformin and clofibrate in maturity onset diabetes mellitus: advantages of combined treatment. Blood glucose, lipoproteins, non-esterified fatty acids, fibrinogen and intermediary metabolites were measured in twenty-two diet failed maturity onset diabetics during a double blind crossover study of metformin (1.7 g/day) or clofibrate (2 g/day) therapy. Patients received combined therapy for a final two month period. Four patients had 12 hour metabolic profiles performed during each treatment period. A more significant improvement in fasting blood glucose and glycosuria occured with metformin and combined therapy. However, clofibrate and combined therapy significantly decreased total and low density lipoprotein cholesterol, total and very low density lipoprotein triglyceride and fibrinogen. Metabolic profiles demonstrated significant elevations of blood lactate and alanine with metformin treatment but these parameters returned to normal with combined therapy. Non-esterified fatty acids and glycerol were significantly lower during combined therapy compared with metformin or clofibrate alone. Despite the recent adverse report on clofibrate, this study indicates that the addition of clofibrate to metformin therapy may have advantages in the management of maturity onset diabetics.


[Participation of cholinergic mechanisms in the regulation of immunological processes]. Chronic administration of cholinomimetic (arecolin, pilocarpin, nicotin) and cholinolytic (bezohexonium, pedifen) drugs produces changes of different directions in the number of rosette-forming cells in the spleen of CBA mice immunized with sheep red blood cells. The analysis performed does not allow the effect of the drugs on immunologic processes to be accounted for by an immediate action on lymphoid cells or by an action of the function of the pituitary-adrenal system.


[Effect of BCNU on the kinetics of the primary immune response in mice]. It was shown in experiments on mice administered the alkylating agent BCNU (1,3-bis/2-chlorethyl/-I-nitrosourea) at a dose of 20 mg/kg 48 or 72 hours following immunization wtih sheep red cells that kinetics of producing antibody-forming cells assumes a wave-like pattern with a sharp alternation of rises and falls in the number of antibody inducers. Analysis of the data obtained allowed a conclusion that BCNU does not affect the recruitment -- transformation of the precursor cells to antibody-forming cells.


H-Y antigen in the teleost.

H-Y antigen in the teleost. H-Y antigen, presumably the product of mammalian testis-determining genes, has been detected in three species of teleost fish, Xiphophorus maculatus. Haplochromis burtoni, and Oryzias latipes, and in hybrids of the genus Tilapia. In X. maculatus H-Y was most readily detected in YY males, suggesting that a genetic determinant of H-Y antigen expression may exist on the teleost Y-chromosome. Although H-Y was detected in males and not in feamles in each of the species that we studied, male heterogamety has not been firmly established for H. burtoni. Thus despite the extreme phlyogenetic conservation of H-Y genes and their association with the Y-chromosome, it remains open to question whether H-Y will always be found in the heterogametic sex, and whether serologically defined H-Y antigen plays any part in the differentiation of the teleost gonad.


Shift from free "small" hepatitis B e antigen to IgG-bound "large" form in the circulation of human beings and a chimpanzee acutely infected with hepatitis B virus. Hepatitis B e antigen (HBeAg) occurs both free and in association with IgG in the circulation of individuals infected with hepatitis B virus (HBV). We determined free and IgG-bound HBeAg forms separately in the serum of humans and a chimpanzee acutely infected with HBV. In a patient with laboratory acquired HBV infection, the proportion of free HBeAg gradually decreased from 89% to 23%. A similar shift from free to IgG-bound form of HBeAg was invariably observed in 5 additional patients with acute Type B hepatitis. In a chimpanzee that had been experimentally inoculated with HBV, free HBeAg appeared first, then gradually and completely shifted to the IgG-bound form. Finally, IgG-bound HBeAg disappeared, and antibody to HBeAg was detectable in the serum. The determination of both free and IgG-bound forms of HBeAg may provide valuable information, because their ratio reflects the stage and prognosis of acute HBV infection.


Analysis of the albino-locus region of the mouse. III. Time of death of prenatal lethals. The stage at which homozygotes die was determined for 28 mutations (general symbol c*) at the albino (c) locus, of which 26 had earlier been found to be probably prenatally lethal. Within each of the mutant stocks, the uterine contents of c*/c(ch) females, made pregnant either by c*/c(ch) males ("Ex" series) or by c(ch)/c(ch) males ("Co" series), were examined between 13 and 17 days postconception. Altogether, 743 females were dissected and 7197 corpora lutea (representing ovulations) counted. In selected stocks, an additional 40 and 13 females were dissected on days seven or nine, respectively.-In each of the 26 presumed prenatally lethal mutants, there was a deficiency of living fetuses in the Ex, as compared with the Co, group. Overall, this deficiency was 23.6% (expectation, 25% c*/c*). All meaningful excesses were in numbers either of moles (death shortly before, during, or just after implantation), or of early preimplantation losses. Homozygotes in none of the mutant stocks die between days nine and 19 postconception. Of 24 c-locus mutants known to be deficiencies since they lack the closely linked Mod-2, 13 clearly kill before implantation, ten around implantation, and one neonatally. The c and Mod-2 loci and the region between them are not needed for intrauterine survival.-There are indications that the distinction between early-preimplantation death and implantation death may, in a general way, be related to length of the deficiency.


Lethals, steriles and deficiencies in a region of the X chromosome of Caenorhabditis elegans. Twenty-one X-linked recessive lethal and sterile mutations balanced by an unlinked X-chromosome duplication have been identified following EMS treatment of the small nematode, Caenorhabditis elegans. The mutations have been assigned by complementation analysis to 14 genes, four of which have more than one mutant allele. Four mutants, all alleles, are temperature-sensitive embryonic lethals. Twelve mutants, in ten genes, are early larval lethals. Two mutants are late larval lethals, and the expression of one of these is influenced by the number of X chromosomes in the genotype. Two mutants are maternal-effect lethals; for both, oocytes made by mutant hermaphrodites are rescuable by wild-type sperm. One of the maternal-effect lethals and two larval lethals are allelic. One mutant makes defective sperm. The lethals and steriles have been mapped by recombination and by complementation testing against 19 deficiencies identified after X-ray treatment. The deficiencies divide the region, about 15% of the X-chromosome linkage map, into at least nine segments. The deficiencies have also been used to check the phenotypes of hemizygous lethal and sterile hermaphrodites.


[Problems in the genetics of stress. IV. A genetic analysis of the level of autonomic reactivity in emotional stress in rats]. A genetic analysis of hypertensive reactions under condition of emotional stress in three inbred strains of rats (Wistar, Sprague-Dowly and August) and their F1 reciprocal hybrids is carried out. Highly significant genotypic differences in the arterial pressure level during emotional stress and no genetic diversity in the basal state were found. Application of our own methos to genetic analysis of incomplete diallelic tables for Griffing's experimental design 1 (model 1) showed an existence of significant additive component of genetic variance in autonomic reactivity under the stress. The role of the stress as a factor of differentiation of the genetic structure of population is discussed.


[Early diagnosis of congenital and infantile strabismus]. Early detection of strabism by the pediatrician is essential for induction of an effective ophthalmologic therapy. Evaluation should not only be done in children with manifest strabism, but also in children prone to develop this disorder like premature-born infants, children with cerebral defects or even children from families with high incidence of strabism.


Concentration of porcine proinsulin-like material in plasma of insulin-treated diabetics in relation to purity of insulin preparations. Porcine proinsulin-like Material (P-PLM) was determined in plasma from 25 juvenile diabetics previously treated for more than six years with crystalline porcine insulin and again after 2--2 1/2 years subsequent treatment with highly purified porcine insulin. As P-PLM in insulin preparations was reduced from 7 mmol/mol insulin to 0.1 mmol/mol insulin, so plasma concentrations of P-PLM were reduced from mean 166 pmol/l (range 34--428) to mean 27 pmol/l (range 13--64) on the same insulin dose. During the same period, the insulin-binding capacity of plasma showed a decrease.


Production of a specific antiserum by synthetic C-terminal fragment of glucagon. Seven rabbits were immunized with a synthetic C-terminal glucagon fragment [15--29] conjugated with bovine serum albumin by means of glutaraldehyde. Antisera for glucagon were produced in all the animals after six injections of the conjugate. One of them revealed a higher titer antiserum (G42), which did not cross react with gut glucagon-like immunoreactive material, secretin, insulin, gastric inhibitory polypeptide or vasoactive intestinal peptide. From the results of inhibition of 125 I-glucagon in binding with the antiserum by various glucagon-related fragments the immunogenic determinant of the antiserum was proved to be in the C-terminal residue of the glucagon molecule, although peptide [17--29] or [21--29] reacted weakly with the antiserum. The plasma glucagon levels measured by antiserum G 42 during an arginine test in five normal subjects were superposed on those obtained by other antiserum (G21), specific for pancreatic glucagon. Furthermore, a comparable standard curve for glucagon was obtained using antiserum G42, when a labelled p-hydroxyphenylacetylated glucagon fragment [15--29] was employed as a tracer. The present study clearly demonstrated that the C-terminal glucagon fragment could yield a specific antiserum for pancreatic glucagon, supporting the proposal that the C-terminal fragment of glucagon is responsible for such specific antisera. Furthermore, it is concluded that immunoassay for glucagon could be performed using the labelled glucagon fragment as a tracer.